In this work, we successfully constructed Mn-coordinated nitrogen–carbon nanoparticles (Mn–N–C NPs) exhibiting multienzyme-like activities. In a bacterial infectious microenvironment, the POD-like and OXD-like activities of Mn–N–C NPs could synergistically trigger the generation of ROS (˙OH and O₂˙⁻), causing oxidative damage to the bacterial cell membrane for killing bacteria. Alternatively, in neutral or weak alkaline normal tissues, the excessive O₂˙⁻ could be converted into O₂ and H₂O₂via the SOD-like ability of Mn–N–C NPs, and subsequently their CAT-like activity catalyzed excess H₂O₂ into H₂O and O₂ for protecting normal cells through the antioxidant defense. Mn–N–C NPs also possessed a good NIR-photothermal performance, which could enhance their POD-like and OXD-like activities. Furthermore, Mn–N–C NPs could facilitate the GSH oxidation process and disrupt the intrinsic balance in the bacterial protection microenvironment with the assistance of H₂O₂, which is beneficial for rapid bacterial death. Undoubtedly, the Mn–N–C NPs + H₂O₂ system showed the highest antibacterial activity when irradiated with an 808 nm laser, destroying the bacterial membrane and causing the efflux of proteins. Moreover, the Mn–N–C NPs + H₂O₂ system was immune to the development of bacterial resistance and could efficiently disrupt the formation of a bacterial biofilm with negligible cytotoxicity and low hemolysis ratio. Finally, Mn–N–C NPs exhibited an excellent antibacterial performance in vivo and could accelerate wound healing without cellular inflammation production. Therefore, due to their significant therapeutic effects, Mn–N–C NPs show great potential in fighting antibiotic-resistant bacteria.