Shugan Jieyu Capsule (SGJYC) has been prescribed to treat primary and secondary depression; however, whether it can benefit depression of patients with coronary heart disease (CHD) remains controversial. This meta-analysis aimed to evaluate the efficacy and safety of SGJYC in treating depression in patients with CHD.A total of 644 CHD patients with depression were selected from China National Knowledge Infrastructure, Wanfang, China Biomedical Database, MEDLINE, the Cochrane library from their inceptions until June, 2021.All patients with CHD or coronary artery disease were confirmed to suffer from depression based on recognized criteria.Patients were assigned randomly to receive SGJYC-based regimens or conventional antidepressants alone.Meta-analysis of 6 studies showed that antidepressants (MD, 2.12; 95% confidence interval [CI], 0.73~3.50) or sertraline (MD, 2.15; 95%CI, 0.61~3.68) significantly alleviated depression level compared to SGJYC; however, SGJYC plus antihypertensive drugs (AHD) (MD, -8.33; 95%CI, -13.90 ~ -2.75) significantly improved depression symptoms compared to AHD. A significant difference in risk of adverse cardiac events (risk ratios [RR], 2.72; 95%CI, 1.07~6.94) between SGJYC and sertraline was detected in patients with simple CHD.SGJYC has a poor effect on depressive symptoms, and the effect of combination with AHD is better than AHD but its efficacy and cardiac safety are inferior to antidepressants.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.