Orchestration　of　enzyme　cascades　in　synthetic　systems　remains　a　major　challenge　for　catalytic　control　in　complex　biological　environments.　Here,　a　zinc-coordinated　tri-enzyme　nanogel　system　(Zn@nGSC)　is　reported　that　mimics　natural　enzymatic　assemblies　by　confining　individual　glucose　oxidase　(GOX),　superoxide　dismutase　(SOD),　and　catalase　(CAT)　within　an　imidazole-functionalized　polymeric　nanogel　matrix.　The　nanogel　is　fabricated　via　mild　in　situ　polymerization　combined　with　Zn2(+)-imidazole　coordination,　yielding　structurally　stable　multi-enzyme　assemblies.　The　engineered　assemblies　demonstrate　simultaneous　preservation　of　enzymatic　activity　and　enhanced　cascade　efficiency　under　thermal　and　proteolytic　stress.　Cascade　reactions　proceed　as　follows:　i)　glucose　is　depleted　by　GOX,　ii)　superoxide　radicals　are　scavenged　by　SOD　to　alleviate　oxidative　stress,　and　iii)　residual　H2O2　is　converted　into　oxygen　by　CAT　in　order　to　mitigate　hypoxia.　Functionally,　Zn@nGSC　restores　redox　balance　and　metabolic　homeostasis,　demonstrated　in　a　murine　model　of　post-pancreatectomy　wound　healing,　with　emphasis　on　treating　hyperglycemia　and　improving　regeneration.　Another　pronounced　advantage　of　Zn@nGSC　treatment　is　its　antibacterial　effect,　which　enhances　angiogenesis,　collagen　deposition,　and　immune　modulation.　Overall,　this　modular　nanoplatform　provides　a　blueprint　for　designing　robust,　bioresponsive　cascade　systems　with　therapeutic　potential　in　metabolically　compromised　microenvironments.