Bacterial infections have become a major danger to public health because of the appearance of the antibiotic resistance. The synergistic combination of multiple therapies should be more effective compared with the respective one alone, but has been rarely demonstrated in combating bacterial infections till now. Herein, oxygen-vacancy molybdenum trioxide nanodots (MoO NDs) are proposed as an efficient and safe bacteriostatic. The MoO NDs alone possess triple-therapy synergistic efficiency based on the single near-infrared irradiation (808 nm) regulated combination of photodynamic, photothermal, and peroxidase-like enzymatic activities. Therein, photodynamic and photothermal therapies can be both achieved under the excitation of a single wavelength light source (808 nm). Both the photodynamic and nanozyme activity can result in the generation of reactive oxygen species (ROS) to reach the broad-spectrum sterilization. Interestingly, the photothermal effect can regulate the MoO NDs to their optimum enzymatic temperature (50 °C) to give sufficient ROS generation in low concentration of H O (100 µm). The MoO NDs show excellent antibacterial efficiency against drug-resistance extended spectrum β-lactamases producing Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA). Animal experiments further indicate that the MoO NDs can effectively treat wounds infected with MRSA in living systems.