Organic　molecule　desalination　with　nanofiltration　has　important　practical　application　significance.　Zwitterion-based　nanofiltration　membranes　(ZNFMs)　with　selective　channels　for　monovalent　salts　have　been　prepared　to　improve　the　separation　performance.　However,　most　ZNFMs　tend　to　be　restricted　by　their　loose　structures,　which　results　in　unsatisfactory　rejection　for　small　molecules　with　sub-200　Da　molecular　weight.　In　this　study,　a　synchronous　modification　strategy　during　the　heat　treatment　of　interfacial　polymerization　was　proposed,　in　which　various　multi-amine　solutions　were　employed　as　the　novel　medium　of　heat　treatment　to　regulate　the　structures　of　ZNFMs.　The　pore　size　distribution　of　membranes　could　be　narrowed　to　a　certain　degree　through　cross-linking　by　corresponding　multi-amines.　The　optimized　ZNFMs　exhibited　excellent　retention　to　small　molecules.　For　example,　the　retention　of　glucose　was　dramatically　increased　to　96.5%.　Meanwhile,　the　ZNFMs　also　had　low　rejection　for　monovalent　salts,　such　as　KCl　(26.7　%).　Consequently,　the　separation　factor　between　glucose　and　KCl　reached　21.2,　which　demonstrated　a　great　potential　for　organic　molecule　desalination　with　sub-200　Da　molecular　weight.　©　2024　Elsevier　B.V.