Objective To explore the efficacy of lipoic acid combined with mecobalamin in the treatment of acute cerebral infarction and its effects on the National Institutes of Health Stroke Scale (NHISS) score and oxidative stress level. Methods A total of 100 patients with acute cerebral infarction who were treated in our hospital from October 2016 to October 2017 were selected and divided into treatment group and control group according to the method of random sampling, with 50 cases in each group. Control group was given mecobalamin, and treatment group was given lipoic acid combined with mecobalamin. The effective rate of treatment was evaluated after 2 weeks. The NHISS score and levels of serum superoxide dismutase (SOD) and serum malondialdehyde (MDA) were compared between the two groups before and after treatment. Results The effective rate (90%) in treatment group was higher than that in control group (P<0.05). The NHISS scores were decreased after treatment, and the decrease in treatment group was greater than that in control group (P<0.05). The levels of serum SOD and serum MDA in the two groups were decreased after treatment, and the decreases were more significant in treatment group (P<0.05). Conclusion Lipoic acid combined with mecobalamin has more exact efficacy in the treatment of acute cerebral infarction than metocobalamine alone. And it can promote the recovery of neurological function and improve the body’s oxidative stress.