Objective To investigate the clinical effect of α-Lipoic Acid combined with Epalrestat in the treatment of diabetic peripheral neuropathy. Methods A total of 100 patients with diabetic peripheral neuropathy diagnosed and treated in our hospital from May 2018 to June 2019 were selected as the research objects. They were divided into the experimental group (50 cases) and the control group (50 cases) according to the random number table method. The control group was treated with Epalrestat, and the experimental group was treated with α-Lipoic Acid combined with Epalrestat. The clinical efficacy, treatment indexes and adverse reactions of the two groups were compared. Results The total effective rate of the experimental group was higher than that of the control group, and the difference was statistically significant (P＜0.05). There were no statistically significant differences in the motor nerve conduction velocity and sensory nerve conduction velocity between the two groups of patients before treatment (P＞0.05). The differences between motor nerve conduction velocity and sensory nerve conduction velocity after treatment in the two groups were statistically significant (P＜0.05). The conduction velocity of median nerve and superficial peroneal nerve in the motor nerve of the experimental group after treatment were higher than those in the control group, the differences were statistically significant (P＜0.05). The conduction velocity of median nerve and superficial peroneal nerve in the sensory nerve of the experimental group were higher than those of the control group, the differences were statistically significant(P＜0.05). There was no significant difference in the total incidence of adverse reactions between the experimental group and the control group (P＞0.05). Conclusion α-Lipoic Acid combined with Epalrestat in the treatment of diabetic peripheral neuropathy can effectively improve the clinical efficacy, can increase the nerve conduction velocity, and the drug safety is high, so it is worthy of popularization and application.