Background: Xinkeshu tablets (XKS), a well-known Chinese patent drug, have been administered to coronary heart disease (CHD) patients with anxiety and depression after percutaneous coronary intervention (PCI). Purpose: This meta-analysis aimed to systematically evaluate the clinical effects of XKS for treating CHD patients with anxiety and depression after PCI. Methods: Randomized controlled trials (RCTs) about XKS alone or combined with conventional drugs for the treatment of CHD patients with anxiety and depression after PCI were retrieved from 7 databases (MEDLINE, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP) Database, Chinese Biomedical Database (CBM) and Wanfang Database) through November 2021. First, the studies were reviewed and screened by two independent assessors according to the eligibility criteria. Second, the methodological quality of the eligible studies was evaluated based on the Cochrane Collaboration's tool for assessing the risk of bias. Subsequently, meta-analysis was performed by using RevMan 5.4 software, and publication bias was evaluated by Stata 12.0 software. Finally, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was applied to rate the quality of the evidence. Results: In total, 11 clinical RCTs involving 1000 patients were included in this study. This meta-analysis found that compared with conventional treatment alone, XKS combined with conventional treatment significantly improved the anxiety scale scores (SMD = -1.97, 95% CI -3.13 to -0.82; p = 0.0008; I = 98%), the depression scores (SMD = -2.80, 95% CI -4.49 to -1.10; p = 0.001; I = 98%), the scores on the Medical Outcomes Study 36 Item Short Form Health Survey (SF36) (MD = 11.22, 95% CI 4.19 to 18.26; p =0.002; I = 95%) and the blood lipid levels of total cholesterol (TC) (MD = -0.38, 95% CI -0.62 to -0.13; p = 0.003; I = 0%) and triglyceride (TG) (MD = -0.31, 95% CI -0.46 to -0.17; p < 0.0001; I = 0%). Conclusion: The current evidence suggests that XKS might benefit CHD patients experiencing anxiety and depression after PCI by helping to improve their depression symptoms, TC and TG blood lipid levels. However, due to insufficient methodological quality of the studies, several risks of bias and inadequate reporting of the clinical data, more rigorous, multicenter, sufficient-sample and double-blind randomized clinical trials are warranted.