Background: Diabetic foot ulcer (DFU) represent a long-term complication of diabetes, associated with significant morbidity and high risk of lower extremity amputation. Considering the greater frequency of this complication in men, the aim of this study was to investigate the gender differences in people with type 2 diabetes (T2DM) and DFU. Methods: This observational study included 203 individuals with T2DM, who were admitted for DFU in a tertiary-care center. Laboratory measurements and clinical assessments, including long-term diabetes complications and risk factors for DFU, were collected from medical records. The study population was divided in 2 groups according to the gender [Male (M), n=109 vs Female (F), n=94]. Results: Compared with the F group, people in M group were significantly younger [M vs F, median (IQR), 61 (57,70) vs 70 (60,78), p<0.001], were more frequently smokers (67.9% vs 34%, p<0.001) and had lower levels of HDL-cholesterol [35.0 (29.0,43.0) vs 44.0 (36.0,54.0), p<0.001]. Significant differences were found between groups in kidney function [estimated Glomerular Filtration Rate (eGFR) 80.4 (55.45,106.5) vs 72.10 (43.35,88.35), p=0.011] and blood count [haemoglobin (HGB) 13.1 (11.9,14.4) vs 11.6 (10.2,12.7), p<0.001]. As compared with F group, a higher proportion of neuropathy (66% vs 41.5%, p<0.001) and combined ulcers (39.5% vs 22.4%, p=0.014) were observed in men, whereas women had a higher rate of phlebolymphatic ulcers (8.2% vs 30.8%, p<0.001). No significant differences were found among other DFU risk factors or clinical features and treatment. Conclusions: In this observational study of people with T2DM and DFU, there were gender differences regarding to clinical features and DFU-related parameters affecting more frequently male sex including age, smoking habit, HDL-cholesterol, kidney function and blood count. Among DFU-related parameters, neuropathy and combined DFU occurred more frequently in men, whereas women were mostly affected by phlebolymphatic ulcers.