OBJECTIVE: To evaluate the clinical efficacy of mecobalamin combined with epalrestat in treating diabetic peripheral neuropathy (DPN) and its effects on inflammatory factors and electromyogram (EMG) indices. METHODS: Data from 100 DPN patients treated at Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital between June 2021 and December 2022 were retrospectively analyzed. Among them, the control group was 45 patients treated with mecobalamin alone. 55 patients treated with epalrestat, in addition to mecobalamin, were the observation group. Outcomes compared between the two groups included the changes in inflammatory factors, EMG indices, oxidative stress markers, blood glucose levels before and after treatment, clinical efficacy, and the incidence of adverse reactions. RESULTS: The observation group showed a significantly higher overall response rate than the control group (P<
0.05). After treatment, the observation group exhibited lower levels of C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), and matrix metalloproteinase-9 (MMP-9) than control group (all P<
0.05). The observation group also demonstrated higher motor nerve conduction velocity (MCV) and sensory nerve conduction velocity (SCV) of the median nerve and nervus peronaeus communis compared to the control group (all P<
0.05). Additionally, the observation group showed lower levels of propylene glycol and higher levels of superoxide dismutase compared to the control group (both P<
0.05). Fasting blood glucose and 2-hour postprandial blood glucose levels in the observation group were significantly lower than those in the control group (P<
0.05). Both groups exhibited a decrease in Michigan Diabetic Neuropathy Scores post-treatment compared to pre-treatment, with the observation group scoring lower than the control group (P<
0.05). No difference was found between the 2 groups in the incidence of adverse reactions (P>
0.05). CONCLUSION: Mecobalamin combined with epalrestat substantially alleviates DPN, improves electromyogram indices, and reduces inflammatory factors and oxidative stress response, without increasing adverse reactions.