BACKGROUND: Heart failure as an advanced cardiac disease has a high incidence and prevalence in all societies nowadays. Many drugs and treatment methods have been discovered for improving heart failure patients' conditions till now in this way melatonin therapy is one of the less-known methods rarely used by clinicians. METHODS: To investigate the positive effect of melatonin on heart failure development, we conducted a systematic review and meta-analysis by searching valid databases with keywords based on the protocol. Based on the eligible criteria, four articles were selected for data synthesis and analysis after scanning the title and/or abstract and reading full-text. RESULTS: As a result of analysis, increasing ejection fraction (Mean difference: 2.39 [-1.82, 6.59] p = 0.27), NYHA (New York Heart Association Functional Class) (Odds ratio: 4.84 [1.00, 23.44] p = 0.05), and significant elevation of quality of life (Mean difference: -5.95 [-9.54, -2.35] p = 0.001) were observed. As the effect of melatonin, fatigue, and NT-Pro BNP were reduced but on the contrary sleep quality, appetite, and FMD (Flow-Mediated Dilation) significantly increased. CONCLUSION: Thus, melatonin, by increasing psychologic parameters and cardiac potency, could be advised as a novel drug for treatment and palliating heart failure patients.