The　development　of　traditional　small　molecule　antibiotics　is　becoming　increasingly　challenging,　and　they　are　no　longer　effective　against　the　growing　number　of　multidrug-resistant　infections.　Therefore,　in　this　study,　polyhexamethylene　biguanide-bismuth　tungstate-poly(vinylpyrrolidone)　nanoparticles　(PHMB-BWO-PVP　NPs)　were　synthesized　to　achieve　effective　treatment　of　drug-resistant　bacterial　infections　through　the　synergistic　chemical/low-temperature　photothermal　therapy　(CT/LT-PTT).　PHMB　was　loaded　on　BWO-PVP　NPs　via　electrostatic　interactions　to　form　PHMB-BWO-PVP　NPs　that　were　stable　in　saline,　phosphate-buffered　saline,　and　Dulbecco’s　modified　Eagle’s　medium.　The　NPs　had　a　zeta　potential　of　+10.6　mV　and　a　particle　size　of　about　45　nm.　Moreover,　the　NPs　were　endowed　with　photothermal　conversion　ability　by　BWO　and　chemical　antimicrobial　capacity　by　PHMB.　Thus,　under　LT-PTT,　the　NPs　accelerated　the　release　of　PHMB,　which　exhibited　excellent　bactericidal　effects　against　methicillin-resistant　Staphylococcus　aureus　and　drug-resistant　Escherichia　coli　through　synergistic　effects,　and　inhibited　the　formation　of　bacterial　biofilms.　Importantly,　PHMB-BWO-PVP　NPs　can　eliminate　skin　abscesses　in　mice　infected　with　drug-resistant　bacteria　via　synergistic　CT/LT-PTT,　induce　the　transformation　of　M1　macrophages　to　M2　macrophages,　promote　collagen　deposition　and　angiogenesis,　and　ultimately　facilitate　wound　tissue　healing.　©　2024　American　Chemical　Society.