Abstract: Objective To analyze the risk factors for the occurrence of lower extremity arteriosclerosis occlusive disease (LEAOD) in patients with diabetic peripheral neuropathy (DPN), and to compare the efficacy and safety of pentoxifylline and beraprost sodium tablets. Methods A total of 140 DPN patients admitted to the First Affiliated Hospital of Henan University of Science and Technology between January 2023 and March 2025 were enrolled, comprising 80 cases with LEAOD (LEAOD group) and 60 cases without LEAOD (non-LEAOD group). Multivariate logistic regression was employed to screen for risk factors. The LEAOD group was then equally randomized to receive either pentoxifylline or beraprost sodium tablets (40 cases each), and the interventional efficacy was evaluated. Results Age ≥ 60 years old, concomitant coronary artery disease, elevated levels of glycated hemoglobin (HbA1c), low density lipoprotein cholesterol (LDL-C) and cystatin C (CysC), as well as decreased adiponectin levels were identified as independent risk factors for LEAOD in DPN patients (P＜0.05). The total effective rate was 87.50% in the pentoxifylline group and 77.50% in the beraprost sodium tablet group, with no statistically significant difference observed between the two groups (P＞0.05). Similarly, the incidence of adverse reactions did not differ significantly between the pentoxifylline group (22.50%) and the beraprost sodium tablet group (27.50%) (P＞0.05). Conclusion Concomitant coronary artery disease and elevated levels of HbA1c, LDL-C and CysC, along with decreased adiponectin levels, are significant risk factors for the occurrence of LEAOD in DPN patients. Both pentoxifylline and beraprost sodium tablets are effective therapeutic options for improving LEAOD. Targeted pharmacological intervention drugs can be selected clinically based on the metabolic-inflammation characteristics of patients.