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Diabetic foot (DF) is a severe and common complication of diabetes mellitus, involving peripheral neuropathy, vascular disease, immune-inflammatory disorders, and impaired tissue repair, with high amputation rates and a heavy medical burden. The Notch1 signaling pathway is highly conserved and participates in regulating cell proliferation, differentiation, apoptosis, angiogenesis, and inflammatory responses. Emerging evidence indicates that dysregulated Notch1 signaling is closely associated with the pathological progression of diabetic foot ulcers (DFU). This review systematically summarizes the role of Notch1 signaling in angiogenesis, inflammation, peripheral neuropathy, and cell fate regulation during DF pathogenesis, and discusses the potential therapeutic strategies targeting Notch1 pathway for DFU. We aim to provide new insights into the molecular mechanism and targeted therapy of DF.Infographic available for this article.