Bacterial infections, especially those caused by antibiotic-resistant Listeria monocytogenes (L. monocytogenes), hinder the healing of scalds in food processing environments. This study developed a high-entropy nanozyme (HEzyme) hydrogel system that exhibited efficient reactive oxygen species (ROS) and photothermal antibacterial effects. The HEzyme was synthesized using a carbon-oxygen-silicon framework-assisted method, incorporating multiple metal species (CoNiCuZnCe). It demonstrated superior catalytic efficiency, generating hydroxyl radicals (•OH) from hydrogen peroxide (H2O2). Exposure to 808 nm irradiation caused a rapid temperature increase, enabling photothermal effect. HEzyme was integrated into a chitosan-based hydrogel microneedle system, which generated ROS and heat when exposed to H2O2 and irradiation. The microneedles, designed for transdermal use, enhanced wound healing and minimized inflammation. In vitro and in vivo tests confirmed that the microneedles effectively eradicated L. monocytogenes and accelerated tissue healing. This approach offers a promising solution for treating antibiotic-resistant infections and promoting healing in scald wounds.