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Given its pathogenesis, the DFU microenvironment is rather complicated and characterized by hyperglycemia, ischemia, hypoxia, hyperinflammation, and persistent infection. However, the current clinical therapies for DFU are dissatisfactory, which drives researchers to turn attention to advanced nanotechnology to address DFU therapeutic bottlenecks. In the last decade, a large number of multifunctional nanosystems based on the microenvironment of DFU have been developed with positive effects in DFU therapy, forming a novel concept of \u201cDFU nanomedicine\u201d. However, a systematic overview of DFU nanomedicine is still unavailable in the literature. This review summarizes the microenvironmental characteristics of DFU, presents the main progress of wound healing, and summaries the state\u2010of\u2010the\u2010art therapeutic strategies for DFU. 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