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Diabetes mellitus (DM) is a chronic, multisystemic metabolic disorder characterized by hyperglycemia resulting from absolute or relative insulin resistance (IR) in peripheral tissues. Diabetic foot ulcers, arising from peripheral arterial disease (a macrovascular complication) and neuropathy (a microvascular complication), represent a major cause of morbidity among diabetic patients. Asprosin is a diabetogenic adipokine involved in glucose metabolism and IR. This study aimed to investigate whether serum asprosin plays a role in the progression of diabetes and the development of diabetic foot ulcers. This comparative cross-sectional observational study included 3 groups: 32 patients with diabetic foot ulcers, 31 patients with type 2 diabetes mellitus (T2DM) without ulcers, and 27 healthy controls. Demographic data (age, gender, family history, body mass index), biochemical parameters, culture results, and serum asprosin levels were evaluated. Serum asprosin concentrations were measured using the Enzyme-Linked Immunosorbent Assay (ELISA) method. Serum asprosin levels differed significantly among the groups (P < .001), being lowest in the control group. Both the diabetic foot and T2DM groups exhibited significantly higher asprosin levels compared to controls (P < .001), although there was no significant difference between the 2 diabetic groups. Additionally, asprosin levels were not significantly affected by the presence of wound infection, positive culture growth, or elevated acute-phase reactants. In this study, serum asprosin was not found to be associated with the development of peripheral complications of diabetes. Further studies with larger cohorts are warranted to clarify the role of asprosin in diabetic vascular and metabolic pathophysiology.