Drug-resistant bacteria caused by the abuse of antibiotics have brought great challenges to antimicrobial therapy. Herein an antibiotic-free polydopamine (PDA) modified metal–organic framework (PDA-FDM-23) with photothermal-enhanced chemodynamic effect was developed for synergistic antibacterial treatment. The PDA-FDM-23 antibacterial agent exhibited high peroxidase-like activity. Moreover, the process was significantly accelerated by consuming glutathione (GSH) to generate more efficient oxidizing Cu⁺. In addition, the photothermal therapy (PTT) derived from PDA improved the chemodynamic therapy (CDT) activity triggering a reactive oxygen species explosion. This PTT-enhanced CDT strategy illustrated 100% antibacterial efficiency against both Staphylococcus aureus and Escherichia coli. Cytotoxicity and hemolysis analyses fully demonstrated the excellent biocompatibility of PDA-FDM-23. Overall, our work highlighted the strong peroxidase catalytic activity, excellent GSH consumption and photothermal performance of PDA-FDM-23, providing a new strategy for antibiotic-free reactive oxygen species (ROS) synergistic sterilization.