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Diabetic wound healing presents serious clinical challenges due to the unique wound microenvironment characterized by hyperglycemia, bacterial infection, excessive oxidative stress, and hypoxia. Herein, a copper peroxide (CuO2)‐coated AuCu bimetallic aerogel is developed that exhibits quadruple enzyme‐mimicking activity and H2O2/O2 self‐supplying to modulate the complex microenvironment of methicillin‐resistant staphylococcus aureus (MRSA)‐infected diabetic wounds. The AuCu@CuO2 aerogels demonstrate favorable photothermal properties and mimic four enzyme‐like activities: peroxidase‐like activity for producing toxic reactive oxygen species; catalase‐like activity for decomposing H2O2 to release O2 to relieve oxidative stress and hypoxia; glucose oxidase‐like activity for reducing excessive blood glucose and glutathione peroxidase‐like activity for balancing abnormal glutathione level. The CuO2 coating facilitates a continuous and adequate in situ production of H2O2 within the mildly acidic infection microenvironment, enabling excellent antibacterial activity and reduced blood glucose levels during the initial treatment of infected diabetic wounds. Furthermore, the engineered AuCu@CuO2 aerogels not only scavenge elevated ROS during the inflammatory phase but also synergistically generate oxygen to promote wound healing. Overall, the AuCu@CuO2 aerogelsmicroenvironment can be activated by the diabetic wound infection microenvironments, alleviating inflammation, reducing hypoxia, lowering blood glucose levels, and enhancing angiogenesis and collagen fiber accumulation, thereby significantly improving diabetic wound healing. The AuCu@CuO2 aerogels demonstrate favorable photothermal properties, four types of enzyme‐like activities, and H2O2/O2 self‐supplying to modulate the complex microenvironment of MRSA‐infected diabetic wounds. The results indicate that the AuCu@CuO2 aerogel can be activated by the microenvironment of diabetic wound infection, alleviating inflammation, reducing hypoxia, lowering blood glucose levels, and enhancing angiogenesis and collagen fiber accumulation, thereby significantly improving diabetic wound healing.