As one of the common reactive oxygen species, H2 O2 has been widely used for combating pathogenic bacterial infections. However, the high dosage of H2 O2 can induce undesired damages to normal tissues and delay wound healing. In this regard, peroxidase-like nanomaterials serve as promising nanozymes, thanks to their positive promotion toward the antibacterial performance of H2 O2 , while avoiding the toxicity caused by the high concentrations of H2 O2 . In this work, ultrasmall Au nanoparticles (UsAuNPs) are grown on ultrathin 2D metal-organic frameworks (MOFs) via in situ reduction. The formed UsAuNPs/MOFs hybrid features both the advantages of UsAuNPs and ultrathin 2D MOFs, displaying a remarkable peroxidase-like activity toward H2 O2 decomposition into toxic hydroxyl radicals (·OH). Results show that the as-prepared UsAuNPs/MOFs nanozyme exhibits excellent antibacterial properties against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria with the assistance of a low dosage of H2 O2 . Animal experiments indicate that this hybrid material can effectively facilitate wound healing with good biocompatibility. This study reveals the promising potential of a hybrid nanozyme for antibacterial therapy and holds great promise for future clinical applications.