<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with Wdesk from Workiva-->
<!--Copyright 2023 Workiva-->
<!--r:451658bd-d88f-4282-9c6a-c1dd52cf3f31,g:9c0f2f52-9e92-4a03-8bd1-6f7b5787d327-->
<xs:schema xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:krys="http://www.krystalbio.com/20230331" xmlns:xbrli="http://www.xbrl.org/2003/instance" xmlns:dtr-types="http://www.xbrl.org/dtr/type/2020-01-21" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" attributeFormDefault="unqualified" elementFormDefault="qualified" targetNamespace="http://www.krystalbio.com/20230331">
  <xs:import namespace="http://fasb.org/srt/2022" schemaLocation="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd"/>
  <xs:import namespace="http://fasb.org/us-gaap/2022" schemaLocation="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd"/>
  <xs:import namespace="http://www.w3.org/1999/xlink" schemaLocation="http://www.xbrl.org/2003/xlink-2003-12-31.xsd"/>
  <xs:import namespace="http://www.xbrl.org/2003/instance" schemaLocation="http://www.xbrl.org/2003/xbrl-instance-2003-12-31.xsd"/>
  <xs:import namespace="http://www.xbrl.org/2003/linkbase" schemaLocation="http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd"/>
  <xs:import namespace="http://www.xbrl.org/dtr/type/2020-01-21" schemaLocation="https://www.xbrl.org/dtr/type/2020-01-21/types.xsd"/>
  <xs:import namespace="http://xbrl.org/2005/xbrldt" schemaLocation="http://www.xbrl.org/2005/xbrldt-2005.xsd"/>
  <xs:import namespace="http://xbrl.sec.gov/dei/2022" schemaLocation="https://xbrl.sec.gov/dei/2022/dei-2022.xsd"/>
  <xs:annotation>
    <xs:appinfo>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="krys-20230331_lab.xml" xlink:role="http://www.xbrl.org/2003/role/labelLinkbaseRef" xlink:type="simple"/>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="krys-20230331_pre.xml" xlink:role="http://www.xbrl.org/2003/role/presentationLinkbaseRef" xlink:type="simple"/>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="krys-20230331_cal.xml" xlink:role="http://www.xbrl.org/2003/role/calculationLinkbaseRef" xlink:type="simple"/>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="krys-20230331_def.xml" xlink:role="http://www.xbrl.org/2003/role/definitionLinkbaseRef" xlink:type="simple"/>
      <link:roleType id="Cover" roleURI="http://www.krystalbio.com/role/Cover">
        <link:definition>0000001 - Document - Cover</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CondensedConsolidatedBalanceSheetsunaudited" roleURI="http://www.krystalbio.com/role/CondensedConsolidatedBalanceSheetsunaudited">
        <link:definition>0000002 - Statement - Condensed Consolidated Balance Sheets (unaudited)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CondensedConsolidatedBalanceSheetsunauditedParenthetical" roleURI="http://www.krystalbio.com/role/CondensedConsolidatedBalanceSheetsunauditedParenthetical">
        <link:definition>0000003 - Statement - Condensed Consolidated Balance Sheets (unaudited) (Parenthetical)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CondensedConsolidatedStatementsofOperationsandComprehensiveLossunaudited" roleURI="http://www.krystalbio.com/role/CondensedConsolidatedStatementsofOperationsandComprehensiveLossunaudited">
        <link:definition>0000004 - Statement - Condensed Consolidated Statements of Operations and Comprehensive Loss (unaudited)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CondensedConsolidatedStatementsofStockholdersEquityunaudited" roleURI="http://www.krystalbio.com/role/CondensedConsolidatedStatementsofStockholdersEquityunaudited">
        <link:definition>0000005 - Statement - Condensed Consolidated Statements of Stockholders' Equity (unaudited)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CondensedConsolidatedStatementsofCashFlowsunaudited" roleURI="http://www.krystalbio.com/role/CondensedConsolidatedStatementsofCashFlowsunaudited">
        <link:definition>0000006 - Statement - Condensed Consolidated Statements of Cash Flows (unaudited)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="Organization" roleURI="http://www.krystalbio.com/role/Organization">
        <link:definition>0000007 - Disclosure - Organization</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPolicies" roleURI="http://www.krystalbio.com/role/SummaryofSignificantAccountingPolicies">
        <link:definition>0000008 - Disclosure - Summary of Significant Accounting Policies</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="NetLossPerShareAttributabletoCommonStockholders" roleURI="http://www.krystalbio.com/role/NetLossPerShareAttributabletoCommonStockholders">
        <link:definition>0000009 - Disclosure - Net Loss Per Share Attributable to Common Stockholders</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="FairValueInstruments" roleURI="http://www.krystalbio.com/role/FairValueInstruments">
        <link:definition>0000010 - Disclosure - Fair Value Instruments</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="BalanceSheetComponents" roleURI="http://www.krystalbio.com/role/BalanceSheetComponents">
        <link:definition>0000011 - Disclosure - Balance Sheet Components</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommitmentsandContingencies" roleURI="http://www.krystalbio.com/role/CommitmentsandContingencies">
        <link:definition>0000012 - Disclosure - Commitments and Contingencies</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="Leases" roleURI="http://www.krystalbio.com/role/Leases">
        <link:definition>0000013 - Disclosure - Leases</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="Capitalization" roleURI="http://www.krystalbio.com/role/Capitalization">
        <link:definition>0000014 - Disclosure - Capitalization</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockBasedCompensation" roleURI="http://www.krystalbio.com/role/StockBasedCompensation">
        <link:definition>0000015 - Disclosure - Stock-Based Compensation</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SubsequentEvents" roleURI="http://www.krystalbio.com/role/SubsequentEvents">
        <link:definition>0000016 - Disclosure - Subsequent Events</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPoliciesPolicies" roleURI="http://www.krystalbio.com/role/SummaryofSignificantAccountingPoliciesPolicies">
        <link:definition>0000017 - Disclosure - Summary of Significant Accounting Policies (Policies)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPoliciesTables" roleURI="http://www.krystalbio.com/role/SummaryofSignificantAccountingPoliciesTables">
        <link:definition>0000018 - Disclosure - Summary of Significant Accounting Policies (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="NetLossPerShareAttributabletoCommonStockholdersTables" roleURI="http://www.krystalbio.com/role/NetLossPerShareAttributabletoCommonStockholdersTables">
        <link:definition>0000019 - Disclosure - Net Loss Per Share Attributable to Common Stockholders (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="FairValueInstrumentsTables" roleURI="http://www.krystalbio.com/role/FairValueInstrumentsTables">
        <link:definition>0000020 - Disclosure - Fair Value Instruments (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="BalanceSheetComponentsTables" roleURI="http://www.krystalbio.com/role/BalanceSheetComponentsTables">
        <link:definition>0000021 - Disclosure - Balance Sheet Components (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="LeasesTables" roleURI="http://www.krystalbio.com/role/LeasesTables">
        <link:definition>0000022 - Disclosure - Leases (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockBasedCompensationTables" roleURI="http://www.krystalbio.com/role/StockBasedCompensationTables">
        <link:definition>0000023 - Disclosure - Stock-Based Compensation (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="OrganizationAdditionalInformationDetail" roleURI="http://www.krystalbio.com/role/OrganizationAdditionalInformationDetail">
        <link:definition>0000024 - Disclosure - Organization - Additional Information (Detail)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPoliciesAdditionalInformationDetail" roleURI="http://www.krystalbio.com/role/SummaryofSignificantAccountingPoliciesAdditionalInformationDetail">
        <link:definition>0000025 - Disclosure - Summary of Significant Accounting Policies - Additional Information (Detail)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPoliciesSummaryofEstimatedUsefulLivesofAssetsDetail" roleURI="http://www.krystalbio.com/role/SummaryofSignificantAccountingPoliciesSummaryofEstimatedUsefulLivesofAssetsDetail">
        <link:definition>0000026 - Disclosure - Summary of Significant Accounting Policies - Summary of Estimated Useful Lives of Assets (Detail)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="NetLossPerShareAttributabletoCommonStockholdersAdditionalInformationDetail" roleURI="http://www.krystalbio.com/role/NetLossPerShareAttributabletoCommonStockholdersAdditionalInformationDetail">
        <link:definition>0000027 - Disclosure - Net Loss Per Share Attributable to Common Stockholders - Additional Information (Detail)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="NetLossPerShareAttributabletoCommonStockholdersScheduleofBasicandDilutedNetLossPerShareandPerUnitDetail" roleURI="http://www.krystalbio.com/role/NetLossPerShareAttributabletoCommonStockholdersScheduleofBasicandDilutedNetLossPerShareandPerUnitDetail">
        <link:definition>0000028 - Disclosure - Net Loss Per Share Attributable to Common Stockholders - Schedule of Basic and Diluted Net Loss Per Share and Per Unit (Detail)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="FairValueInstrumentsSummaryofCashCashEquivalentsandAvailableforSaleSecuritiesDetail" roleURI="http://www.krystalbio.com/role/FairValueInstrumentsSummaryofCashCashEquivalentsandAvailableforSaleSecuritiesDetail">
        <link:definition>0000029 - Disclosure - Fair Value Instruments - Summary of Cash, Cash Equivalents and Available-for-Sale Securities (Detail)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="FairValueInstrumentsSummaryofCashCashEquivalentsandAvailableforSaleSecuritiesDetail_1" roleURI="http://www.krystalbio.com/role/FairValueInstrumentsSummaryofCashCashEquivalentsandAvailableforSaleSecuritiesDetail_1">
        <link:definition>0000029 - Disclosure - Fair Value Instruments - Summary of Cash, Cash Equivalents and Available-for-Sale Securities (Detail)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="BalanceSheetComponentsScheduleofPropertyandEquipmentNetDetail" roleURI="http://www.krystalbio.com/role/BalanceSheetComponentsScheduleofPropertyandEquipmentNetDetail">
        <link:definition>0000030 - Disclosure - Balance Sheet Components - Schedule of Property and Equipment, Net (Detail)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="BalanceSheetComponentsAdditionalInformationDetail" roleURI="http://www.krystalbio.com/role/BalanceSheetComponentsAdditionalInformationDetail">
        <link:definition>0000031 - Disclosure - Balance Sheet Components - Additional Information (Detail)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="BalanceSheetComponentsScheduleofAccruedExpensesAndOtherCurrentLiabilitiesDetail" roleURI="http://www.krystalbio.com/role/BalanceSheetComponentsScheduleofAccruedExpensesAndOtherCurrentLiabilitiesDetail">
        <link:definition>0000032 - Disclosure - Balance Sheet Components - Schedule of Accrued Expenses And Other Current Liabilities (Detail)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommitmentsandContingenciesAdditionalInformationDetail" roleURI="http://www.krystalbio.com/role/CommitmentsandContingenciesAdditionalInformationDetail">
        <link:definition>0000033 - Disclosure - Commitments and Contingencies - Additional Information (Detail)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="LeasesMinimumcommitmentsDetails" roleURI="http://www.krystalbio.com/role/LeasesMinimumcommitmentsDetails">
        <link:definition>0000034 - Disclosure - Leases - Minimum commitments (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="LeasesMinimumcommitmentsDetails_1" roleURI="http://www.krystalbio.com/role/LeasesMinimumcommitmentsDetails_1">
        <link:definition>0000034 - Disclosure - Leases - Minimum commitments (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="LeasesScheduleofSupplementalCondensedConsolidatedBalanceSheetInformationRelatedtoLeasesDetails" roleURI="http://www.krystalbio.com/role/LeasesScheduleofSupplementalCondensedConsolidatedBalanceSheetInformationRelatedtoLeasesDetails">
        <link:definition>0000035 - Disclosure - Leases - Schedule of Supplemental Condensed Consolidated Balance Sheet Information Related to Leases (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="LeasesLeaseexpenseDetails" roleURI="http://www.krystalbio.com/role/LeasesLeaseexpenseDetails">
        <link:definition>0000036 - Disclosure - Leases - Lease expense (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CapitalizationAdditionalInformationDetail" roleURI="http://www.krystalbio.com/role/CapitalizationAdditionalInformationDetail">
        <link:definition>0000037 - Disclosure - Capitalization - Additional Information (Detail)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockBasedCompensationAdditionalInformationDetail" roleURI="http://www.krystalbio.com/role/StockBasedCompensationAdditionalInformationDetail">
        <link:definition>0000038 - Disclosure - Stock-Based Compensation - Additional Information (Detail)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockBasedCompensationScheduleofCompanysStockOptionActivityDetail" roleURI="http://www.krystalbio.com/role/StockBasedCompensationScheduleofCompanysStockOptionActivityDetail">
        <link:definition>0000039 - Disclosure - Stock-Based Compensation - Schedule of Company's Stock Option Activity (Detail)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockBasedCompensationSummaryofStockBasedCompensationExpenseRelatedtoIssuanceofStockOptionAwardsandRestrictedStockAwardsDetail" roleURI="http://www.krystalbio.com/role/StockBasedCompensationSummaryofStockBasedCompensationExpenseRelatedtoIssuanceofStockOptionAwardsandRestrictedStockAwardsDetail">
        <link:definition>0000040 - Disclosure - Stock-Based Compensation - Summary of Stock Based Compensation Expense Related to Issuance of Stock Option Awards and Restricted Stock Awards (Detail)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockBasedCompensationFairValueofStockOptionsValuationAssumptionsDetail" roleURI="http://www.krystalbio.com/role/StockBasedCompensationFairValueofStockOptionsValuationAssumptionsDetail">
        <link:definition>0000041 - Disclosure - Stock-Based Compensation - Fair Value of Stock Options, Valuation Assumptions (Detail)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockBasedCompensationScheduleofCompanysStockActivityDetails" roleURI="http://www.krystalbio.com/role/StockBasedCompensationScheduleofCompanysStockActivityDetails">
        <link:definition>0000042 - Disclosure - Stock-Based Compensation - Schedule of Company's Stock Activity (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
    </xs:appinfo>
  </xs:annotation>
  <xs:element id="krys_MilestonesDomain" abstract="true" name="MilestonesDomain" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="krys_EstimatedUsefulLivesOfAssetsTableTextBlock" abstract="false" name="EstimatedUsefulLivesOfAssetsTableTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:textBlockItemType"/>
  <xs:element id="krys_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedForfeitureRate" abstract="false" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedForfeitureRate" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="krys_ASTRAFacilityMember" abstract="true" name="ASTRAFacilityMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="krys_StockIncentivePlanMember" abstract="true" name="StockIncentivePlanMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="krys_AccruedPayrollAndBenefits" abstract="false" name="AccruedPayrollAndBenefits" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="krys_ScheduleOfSupplementalCondensedConsolidatedBalanceSheetInformationRelatedToLeasesTableTextBlock" abstract="false" name="ScheduleOfSupplementalCondensedConsolidatedBalanceSheetInformationRelatedToLeasesTableTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:textBlockItemType"/>
  <xs:element id="krys_ManufacturingEquipmentMember" abstract="true" name="ManufacturingEquipmentMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="krys_SaleOfStockRemainingAvailableIssuanceAmount" abstract="false" name="SaleOfStockRemainingAvailableIssuanceAmount" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="krys_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorizedPeriodIncreasePercent" abstract="false" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorizedPeriodIncreasePercent" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:pureItemType"/>
  <xs:element id="krys_PeriphaGenMember" abstract="true" name="PeriphaGenMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="krys_MilestoneOneMember" abstract="true" name="MilestoneOneMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="krys_RemainingCommitmentAmount" abstract="false" name="RemainingCommitmentAmount" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="krys_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVest" abstract="false" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVest" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:pureItemType"/>
  <xs:element id="krys_InterestIncomeExpenseAndOtherNonoperatingNet" abstract="false" name="InterestIncomeExpenseAndOtherNonoperatingNet" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="krys_AccruedPreclinicalAndClinicalExpenses" abstract="false" name="AccruedPreclinicalAndClinicalExpenses" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="krys_ClinicalSupplyAgreementMember" abstract="true" name="ClinicalSupplyAgreementMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="krys_LongTermMarketableSecuritiesMember" abstract="true" name="LongTermMarketableSecuritiesMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="krys_AccruedExpensesAndOtherCurrentLiabilities" abstract="false" name="AccruedExpensesAndOtherCurrentLiabilities" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="krys_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageExercisePrice" abstract="false" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageExercisePrice" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:perShareItemType"/>
  <xs:element id="krys_CashCashEquivalentsAndDebtSecuritiesAvailableForSale" abstract="false" name="CashCashEquivalentsAndDebtSecuritiesAvailableForSale" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="krys_IncreaseDecreaseAccruedLegalSettlementAndInProcessResearchAndDevelopment" abstract="false" name="IncreaseDecreaseAccruedLegalSettlementAndInProcessResearchAndDevelopment" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="krys_SaleOfStockAggregateOfferingPrice" abstract="false" name="SaleOfStockAggregateOfferingPrice" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="krys_CashCashEquivalentsAndDebtSecuritiesAvailableForSaleAmortizedCost" abstract="false" name="CashCashEquivalentsAndDebtSecuritiesAvailableForSaleAmortizedCost" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="krys_LesseeOperatingLeaseLiabilityToBePaidAfterYearFour" abstract="false" name="LesseeOperatingLeaseLiabilityToBePaidAfterYearFour" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="krys_IncreaseDecreaseInLeaseLiability" abstract="false" name="IncreaseDecreaseInLeaseLiability" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="krys_NumberOfMilestones" abstract="false" name="NumberOfMilestones" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="krys_LabEquipmentMember" abstract="true" name="LabEquipmentMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="krys_LitigationSettlementMilestonePaymentsSalesThreshold" abstract="false" name="LitigationSettlementMilestonePaymentsSalesThreshold" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="krys_LitigationSettlementTotalConsideration" abstract="false" name="LitigationSettlementTotalConsideration" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="krys_MilestonesAxis" abstract="true" name="MilestonesAxis" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrldt:dimensionItem" type="xbrli:stringItemType"/>
  <xs:element id="krys_NonEmployeeStockOptionMember" abstract="true" name="NonEmployeeStockOptionMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="krys_A2017IPOStockPlanMember" abstract="true" name="A2017IPOStockPlanMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="krys_PlacementSharesMember" abstract="true" name="PlacementSharesMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="krys_IncentiveStockOptionsMember" abstract="true" name="IncentiveStockOptionsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="krys_SignificantAccountingPoliciesLineItems" abstract="true" name="SignificantAccountingPoliciesLineItems" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="krys_ATMProgramMember" abstract="true" name="ATMProgramMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="krys_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAggregateIntrinsicValueAbstract" abstract="true" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAggregateIntrinsicValueAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="krys_MilestoneThreeMember" abstract="true" name="MilestoneThreeMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="krys_SignificantAccountingPoliciesTable" abstract="true" name="SignificantAccountingPoliciesTable" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrldt:hypercubeItem" type="xbrli:stringItemType"/>
  <xs:element id="krys_MilestoneTwoMember" abstract="true" name="MilestoneTwoMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="krys_PublicOfferingMember" abstract="true" name="PublicOfferingMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="krys_AccruedConstructionInProgressCurrent" abstract="false" name="AccruedConstructionInProgressCurrent" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
</xs:schema>
