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The delayed wound closure of ulcer sites resulting from vascular damage and neutrophil dysfunction facilitates bacterial infection. Once drug resistance occurs or bacterial biofilm is formed, conventional therapy tends to fail and amputation is unavoidable. Therefore, effective antibacterial treatment beyond antibiotics is of utmost importance to accelerate the wound healing process and prevent amputation. Considering the complexity of multidrug resistance, biofilm formation, and special microenvironments (such as hyperglycemia, hypoxia, and abnormal pH value) at the infected site of DFU, several antibacterial agents and different mechanisms have been explored to achieve the desired outcome. The present review focuses on the recent progress of antibacterial treatments, including metal\u2010based medications, natural and synthesized antimicrobial peptides, antibacterial polymers, and sensitizer\u2010based therapy. 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