Self-management intervention is an important component of disease management in patients with heart failure. It can improve heart failure knowledge, quality of life, and heart failure-related hospitalizations of heart failure patients. However, studies on the effect of two self-management interventions tasks have reported conflicting results. This study conducted an up-to-date systematic review of the literature to evaluate the effects of self-management interventions on heart failure knowledge, quality of life, and heart failure-related hospitalizations in patients with heart failure. Systematic review and meta-analysis. We searched PubMed, Embase, Web of Science, Cochrane Library, and the references of articles in 14th December 2019. The study characteristics included: authors, year, country, sample size, mean age of patients with heart failure, duration of intervention, recruitment and intervention delivery, interventions based on self-efficacy theory, cognitive behavioral therapy, disease management, self-care education. The risk of bias for each study was assessed independently by two investigators based on the Cochrane Handbook. This study used Revman to analyze different research outcomes. The fixed-effect model was used in the absence of significant heterogeneity or low heterogeneity, and if the heterogeneity was high, the random effect model was used. A total of 4977 publications were retrieved in this study. After eliminating duplicates and screening for titles and abstracts, 209 articles were retrieved for full-text evaluation. Finally, a total sample size analyzed across 15 randomized controlled trials was 2630 participants. This study showed that self-management interventions significantly improved heart failure knowledge (0.61, 95% confidence interval (CI) 0.27–0.95, p = 0.0004), quality of life (0.20, 95% CI 0.02–0.38, p = 0.03), and heart failure-related hospitalization (OR 0.40, 95% CI 0.29 to 0.55, p<0.00001) in patients with heart failure. This study reveals the beneficial effects of self-management interventions on heart failure knowledge, quality of life, and heart failure-related hospitalization in patients with heart failure. Therefore, high quality randomized controlled designs are needed to explore the optimal self-management interventions for patients with heart failure. Tweetable abstract: This study reveals self-management interventions can improve heart failure knowledge, quality of life, and reduced heart failure-related hospitalization.