Abstract: To address the microenvironment characteristics of diabetic wounds, this study developed a glucose-responsive cascade composite hydrogel system. Zeolitic imidazolate framework-8 (ZIF-8) was employed as a functional carrier to encapsulate glucose oxidase (GOx) and nitric oxide precursor L-arginine (L-Arg), forming glucose-responsive functional nanoparticles (GZA NPs). The composite hydrogel (GZA-Gel) was fabricated through photo-crosslinking of methacrylated hyaluronic acid (HAMA) and methacrylated sulfobetaine (SBMA) matrices integrated with GZA NPs. Under high glucose concentration (20 mmol/L), GOx catalyzed glucose oxidation to establish a weakly acidic microenvironment, triggering ZIF-8 decomposition for sequential release of Zn²⁺ and L-Arg. This initiated a cascade reaction generating nitric oxide (NO) and hydrogen peroxide (H₂O₂), achieving cumulative Zn²⁺ release of 79.61%, with H₂O₂ and NO concentrations reaching 6.28 mmol/L and 6.05 μmol/L, respectively. Antibacterial tests demonstrated 95.98% and 93.34% inhibition rates against Escherichia coli and Staphylococcus aureus. Remarkably, GZA-Gel exhibited excellent biocompatibility and significantly enhanced wound healing efficacy, providing a promising therapeutic platform for diabetic wound management.