Objective To compare the multidimensional clinical characteristics of patients with Wagner grade 4-5 diabetic foot (DF) according to the severity of lower extremity atherosclerotic occlusive disease and gender, and to provide clinical evidence for DF wound repair and comprehensive management. Methods Patients with DF who were admitted between January 2021 and June 2025 were enrolled. Eligible patients were included according to predefined inclusion and exclusion criteria. Data collected included general information (demographic characteristics, diabetes-related conditions, comorbidities, and risk factors), clinical indicators (laboratory results obtained within 48 hours of admission), and immune-inflammatory indices. The immune-inflammatory indices were calculated from ratios or weighted relationships among blood cell subsets based on laboratory findings within 48 hours after admission, and were used to reflect inflammatory status, immune profile, and nutritional status. According to lower extremity CT angiography findings, patients were divided into a non-significant stenosis group (patent trunk arteries or luminal stenosis <99%) and a diffuse occlusion group (multisegment trunk artery occlusion or luminal stenosis ≥99%). Univariate analysis was first performed, and variables (general information and clinical indicators) with significant differences were further assessed using logistic regression. In addition, the above indicators were compared between male and female patients. Results A total of 522 patients with DF were initially enrolled, and 104 patients were finally included in the analysis according to the selection criteria, including 73 males and 31 females. Based on lower extremity blood flow status, 44 patients were assigned to the non-significant stenosis group and 60 to the diffuse occlusion group. Among the 104 patients, 68 underwent amputation (65.38%), including 30 cases (44.1%) in the non-significant stenosis group and 38 cases (55.9%) in the diffuse occlusion group; the difference in amputation rate between the two groups was not significant (χ2=0.264, P=0.608). Univariate analysis showed that, compared with the non-significant stenosis group, the diffuse occlusion group had a higher proportion of female patients, older age, lower body mass index (BMI), and a higher prevalence of coronary heart disease. Laboratory examination showed lower neutrophil count, fasting blood glucose, and glycated hemoglobin, but higher hemoglobin and albumin levels in the diffuse occlusion group. Among the immune-inflammatory indices, only the prognostic nutritional index was significantly higher. All of the above differences were significant (P<0.05). logistic regression analysis further showed that older age, female, coexisting coronary heart disease, higher neutrophil count, lower BMI, and higher hemoglobin level were independently associated with diffuse occlusion (P<0.05). Compared with female patients, male patients were younger and had a higher proportion of smokers. In laboratory examination, male patients had lower absolute lymphocyte counts but higher hemoglobin, total bilirubin, indirect bilirubin, and procalcitonin levels. Among the immune-inflammatory indices, the platelet-to-lymphocyte ratio and monocyte-to-lymphocyte ratio were significantly higher. These differences were all significant (P≤0.05). Conclusion Patients with Wagner grade 4-5 DF with different lower extremity blood flow status exhibit significant differences in cardiovascular comorbidities, nutritional status, and inflammatory profiles. In addition, gender-related differences are also observed in vascular lesion characteristics, nutritional status, and inflammatory response. Therefore, comprehensive evaluation incorporating blood flow status, laboratory indicators, and gender-specific characteristics is warranted to develop more individualized treatment strategies, improve limb salvage, and optimize overall prognosis.