Effective clinical management of infected wounds remains challenging due to the transient efficacy and resistance-inducing nature of conventional antibiotics. Multifunctional dressings capable of sustained drug release and microenvironment modulation are urgently needed. Herein, we present a smart thermosensitive hydrogel based on metal–organic framework nanozymes and an antibacterial agent, integrating vancomycin-loaded quasi-MIL-53 (Van@QMIL-53) into a biocompatible chitosan network to form a synergistic triple-action antibacterial system (VQCG). QMIL-53 exhibits enhanced catalytic activity and drug-loading capacity. The chitosan matrix enables sustained drug release and provides ideal wound management properties, including thermosensitivity, excellent swelling capacity, antioxidant activity, and skin adhesion. In vitro, the hydrogel demonstrates potent antibacterial activity against P. aeruginosa and methicillin-resistant S. aureus ( MRSA ). In vivo, its therapeutic efficacy was evaluated in a murine model of wounds co-infected with MRSA and P. aeruginosa. The hydrogel significantly accelerated wound healing by simultaneously eradicating pathogens, scavenging excess reactive oxygen species, and alleviating inflammation, as evidenced by downregulated Tumor Necrosis Factor-alpha (TNF-α) and upregulated Arginase-1 (Arg-1) expression. This work establishes a versatile MOF-hydrogel platform, offering a promising strategy for advanced wound dressings that synergistically address infection, oxidative stress, and tissue repair.