Cell　membranes　selectively　regulate　molecular　transport　and　interactions　via　the　amphiphilic　nature　of　phospholipid　bilayers,　ensuring　cellular　homeostasis.　Inspired　by　this　natural　mechanism,　we　designed　oxidation-responsive　Poly(butylene　furandicarboxylate-co-thiodiglycolate)　(PBFTd)　polyesters　with　controllable　degradation　profiles,　whose　molecular　chain　hydrophilicity　can　be　precisely　modulated　under　mild　oxidative　conditions.　Through　copolymerization　of　thiodiacetic　acid　with　2,5-furandicarboxylic　acid,　the　resulting　PBFTd　polyesters　demonstrate　tunable　melting　temperatures　(51.4–153.1　°C),　exceptional　mechanical　properties　(tensile　strength　＞35　MPa),　and　superior　oxygen　barrier　properties　outperforming　most　degradable　materials.　When　the　content　of　thiodiacetic　acid　in　PBOFTd　exceeds　40　%,　obvious　enzymatic　degradation　can　be　observed.　Controlled　oxidation　using　H2O2　completely　converts　thioether　linkages　to　hydrophilic　sulfone/sulfoxide　groups.　PBFTd　exhibit　intrinsic　hydrolytic　degradability,　showing　3–8　%　weight　loss　after　56　days,　which　increases　to　3.9–28.1　%　upon　controlled　oxidation.　Fukui　function　analysis　and　Density　functional　theory　(DFT)　calculations　elucidate　the　hydrolysis　mechanism,　while　distortion/interaction　analysis　reveal　that　the　reaction　energy　barrier　is　predominantly　governed　by　both　the　substituent　effects　on　ester　bonds　and　the　overall　polymer　hydrophilicity.　The　PBFTd60　with　a　copolymer　content　of　60　%　of　thiodiacetic　acid　demonstrates　potent　anticancer　efficacy　through　sustained　release　of　cytotoxic　degradation　products　and　effective　Reactive　Oxygen　species　(ROS)　scavenging,　showing　superior　and　prolonged　cytotoxicity　compared　to　thiodiacetic　acid　monomer.　This　study　establishes　a　novel　oxidation-mediated　strategy　for　designing　controllable　degradable　polymers,　offering　significant　potential　for　advanced　biomedical　applications.　©　2025