Trimetazidine has been reported to benefit patients with heart failure (HF) and angina. The impact of trimetazidine on non-ischemic HF remains unclear. We reviewed clinical trials to investigate whether trimetazidine could improve exercise endurance, life quality, and heart function in non-ischemic HF patients. We searched the Cochrane Central Register of Controlled Trials, EMBASE, PubMed, and Web of science for randomized clinical trials published before April 30th, 2020; Studies limited to patients with non-ischemic HF, aged \ge18 years, comparing trimetazidine with conventional therapy with/without placebo. Outcome measurements included primary outcomes (6 minutes walking test (6-MWT)) and secondary outcomes (life quality scores, echocardiography parameters, biomarker, peak oxygen consumption). The follow-up period was longer than three months. This study was registered with international prospective register of systematic reviews (PROSPERO) (CRD42020182982). Six studies with 310 cases were included in this research. Trimetazidine significantly improved 6-MWT (weighted mean difference (WMD) = 48.51 m, 95% confidence interval (CI) [29.41, 67.61], p 0.0001, I{}^2 = 0%), left ventricle ejection fraction (LVEF) (WMD = 3.09%, 95% CI [1.09, 5.01], p = 0.002, I{}^2 = 0%) at 3 months, and LVEF (WMD = 6.09%, 95% CI [3.76, 8.42], p 0.0001, I{}^2 = 12%) at 6 months. Furthermore, it reduced peak oxygen consumption (WMD = –2.24 mL/kg per minute, 95% CI [–4.09, –0.93], p = 0.02). This meta-analysis suggested that trimetazidine might be an effective strategy for improving exercise endurance and cardiac function in patients with non-ischemic HF.