Objective <p>This study assessed serum Adiponectin (APN) and Soluble Intercellular Adhesion Molecule-1 (sICAM-1) levels in diabetic foot ulcer (DFU) patients for evaluating disease severity and prognosis.</p> Methods <p>In this retrospective cohort study, 92 DFU patients were assessed during a 6-month outcome evaluation period and categorized by ulcer healing into good prognosis (healed, <i>n</i> = 50) or poor prognosis (unhealed, <i>n</i> = 42). Serum APN and sICAM-1 levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA) and and analyzed for correlations with disease severity and infection grades. Receiver Operating Characteristic (ROC) curves evaluated their predictive value for poor prognosis.</p> Results <p>Serum APN was negatively correlated with infection and disease severity, whereas sICAM-1 exhibited a positive correlation. The good prognosis group had significantly higher APN and lower sICAM-1 levels compared to the poor prognosis group. Both biomarkers predicted poor prognosis: APN (Area Under the Curve (AUC) = 0.765), sICAM-1 (AUC = 0.841). Combining both markers yielded an AUC of 0.853.</p> Conclusion <p>Serum APN and sICAM-1 levels are associated with DFU severity and prognosis, supporting their potential as predictive biomarkers in clinical practice.</p> Clinical trial number <p>Not applicable.</p>