The purpose of this study was to evaluate whether the efficacy of Tongxinluo-mecobalamin combination treatment on diabetic peripheral neuropathy (DPN) is superior to that of treatment with mecobalamin alone. Literature search on PubMed, Excerpta Medica database, Cochrane Central Register of Controlled Clinical Trials database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Wanfang database, and Weipu database was performed up to July 2016. Risk ratio (RR) and its 95% confidence interval (CI) were calculated to assess the dichotomous data, whereas the weighted mean difference (WMD) and its 95% CI were used to assess the continuous data. A total of 13 studies including 1087 participants (546 received the combination treatment, 541 received the mecobalamin treatment) were included for meta-analysis. The overall effect size (RR = 1.52, 95% CI: 1.38-1.67, P < 0.00001) revealed that the effective rate of Tongxinluo-mecobalamin combination treatment was significantly higher than that of mecobalamin treatment in treating DPN. Furthermore, the effects of Tongxinluo-mecobalamin combination treatment on the improvement of median nerve motor conduction velocity (MCV) (WMD = 7.16, 95% CI: 3.72-10.60, P < 0.00001), median nerve sensory conduction velocity (SCV) (WMD = 9.07, 95% CI: 5.24-12.89, P < 0.00001), peroneal nerve MCV (WMD = 6.63, 95% CI: 2.27-11.00, P = 0.003), and peroneal nerve SCV (WMD = 4.59, 95% CI: 1.60-7.59, P = 0.003) were superior to those of mecobalamin treatment. These results suggest that Tongxinluo-mecobalamin combination treatment is more efficacious for DPN than mecobalamin treatment alone.