Background: Immune dysfunction exacerbates the progression of heart failure, prompting the use of immunomodulatory drugs to regulate both immune and cardiac function of patients with heart failure. However, the existing therapeutic results are controversial. Therefore, this study aims to systematically evaluate the influence of immunomodulatory drugs on immune and cardiac function in patients with heart failure. Methods: A computerized search was performed on randomized controlled trials (RCTs) related to immunotherapy drugs in patients with heart failure published in Wanfang, China National Knowledge Infrastructure (CNKI), PubMed, Embase, Web of Science, and other databases from inception to November 2023. Quality assessment was performed using the Cochrane Manual of Systematic Review 5.3, and meta -analysis and sensitivity analysis were carried out using Stata 15.0. Results: 11 studies were included in this meta -analysis. Among patients with heart failure treated with immunomodulatory drugs, left ventricular end -diastolic dimension (LVEDD) [standardized mean difference (SMD) = -0.35, 95% confidence interval (CI): -0.66 similar to-0.04], left ventricular end -systolic diameter (LVESD) [SMD = -0.27, 95% CI: -0.45 similar to-0.10], high sensitivity C reactive protein (hsCRP) [SMD = -1.38, 95% CI: -2.09 similar to-0.67], brain natriuretic peptide (BNP) [SMD = -0.43, 95% CI: -0.72 similar to-0.15], tumor necrosis factor-alpha (TNF-alpha) [SMD = -0.73, 95% CI: -1.12 similar to-0.33], interleukin-6 (IL -6) [SMD = -0.71, 95% CI: -0.87 similar to-0.55) ], interleukin-1 beta (IL-1 beta) [SMD = -0.58, 95% CI: -0.78 similar to-0.37] and quality of life scores (SMD = -0.32, 95% CI: -0.61 similar to-0.0.04) were significantly inferior compared to the control group. Conversely, left ventricular ejection fraction (LVEF) [SMD = 0.62, 95% CI: 0.20 similar to 1.05] and 6 -minute walking distance (6MWD) [SMD = 0.89, 95% CI: 0.58 similar to 1.21] were higher than the control group; There was no significant difference in interleukin-10 (IL -10) [SMD = 0.31, 95% CI: -0.26 similar to 0.88] or adverse events (OR = 1.15, 95% CI: 0.64 similar to 2.05) between the two groups. Conclusion: Immunomodulatory drugs can safely improve cardiac function, motor function, immune function, and quality of life in patients with heart failure.