O-linked β-D-N-acetylglucosamine (O-GlcNAc) modification represents a common form of posttranslational glycosylation orchestrated by two pivotal enzymes, namely, O-GlcNAc transferase and O-GlcNAcase. In recent years, emerging research has revealed a significant association between O-GlcNAc modification and the pathogenesis of diabetic foot ulcers (DFUs). Elevated O-GlcNAc levels under high-glucose conditions contribute to the pathogenesis of DFUs by modifying specific proteins, which are implicated in peripheral neuropathy, peripheral vascular disease, and impaired chronic wound healing. This process includes prolonged inflammation, compromised granulation tissue formation, disordered re-epithelialization, and blocked tissue remodelling. This review focuses on the pathogenesis of DFUs and on the correlation between protein O-GlcNAc modification and DFUs, offering potential new insights for the diagnosis and treatment of this condition.