Objective To discuss the effect of α-lipoic acid combined with epalrestat on patients with type 2 diabetes mellitus (T2DM) and diabetes peripheral neuropathy (DPN), and analyze its effects on electromyography, the serum inflammatory factors and hemorheological indicators. Methods According to random number table method, 84 T2DM patients with DPN admitted to the First Affiliated Hospital of Guangxi University of Science and Technology from September 2021 to September 2023 were divided into control group (treated with epalrestat) and observation group (treated with α-lipoic acid and epalrestat), with 42 cases in each group. The indicators of electromyogram (EMG), inflammatory factors and hemorheology were compared between the two groups. Results After treatment, the motor nerve conduction velocity (MCV) and sensory nerve conduction velocity (SCV) levels of median and common peroneal nerve in the two groups of patients increased, and the observation group were higher than the control group (all P<0.05). After treatment, The hypersensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) in two groups of patients were lower than before treatment, and the observation group were lower than the control group (all P<0.05). After treatment, whole blood high tangential viscosity, whole blood low tangential viscosity and plasma viscosity values in two groups of patients were lower than before treatment, and the observation group were lower than those in the control group (all P<0.05). Conclusion α-lipoic acid combined with epalrestat is effective in the treatment of T2DM and DPN patients, which can improve nerve conduction velocity, inhibit inflammatory response and regulate hemorheology