〔Abstract〕 Objective To evaluate the effi cacy and safety of the combination of Chaihu-Shugan-San (CSS) and antidepressants on depression. Methods Randomized controlled trials (RCTs) on the efficacy and safety of the combination of CSS and antidepressants versus antidepressants alone for the treatment of depression were retrieved by searching the China National Knowledge Infrastructure database, the Wanfang database, VIP, PubMed, Medline and Cochrane Library. Data analyses were performed using Review Manager 5.2 and STATA 11.0. Results Eight RCTs including 562 patients were included in the present meta-analysis. The results revealed signifi cant differences in the HAMD score (OR = -2.86, 95 % CI: -5.23 ~ -0.48, P = 0.02), which suggested the effects in the CSS plus antidepressant group were better than that in the antidepressant alone group. The results revealed signifi cant differences in the therapeutic effects (OR = 2.96, 95 % CI: 1.69 ~ 5.18, P = 0.0001), which suggested the effects in the CSS plus antidepressant group were better than that in the antidepressant alone group. The results revealed signifi cant differences in the TESS score (OR = -0.65, 95 % CI: -1.02 ~ -0.28, P = 0.0006), and the TESS score in the CSS plus antidepressant group was lower than that in the antidepressant alone group. Conclusion CSS combined with antidepressants are more effective and safety compared with antidepressants alone in the treatment of depression. However, our fi ndings should be further verifi ed based on a larger sample size and prospective randomized controlled trial.