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Abstract Background Cardiotoxicity is one of the most common adverse events of the chemotherapy. Physical exercise was shown to be cardioprotective. We aim to estimate the efficacy and safety of exercise in cancer patients receiving cardiotoxic chemotherapy. Methods We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, SCOPUS, Cochrane, Clinical Trials.gov, and MedRxiv through July 17th, 2023. We used RevMan V. 5.4 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI). PROSPERO ID: CRD42023460902. Results We included thirteen RCTs with a total of 952 patients. Exercise significantly increased VO2 peak (MD: 1.95 with 95% CI [0.59, 3.32], P = 0.005). However, there was no significant effect regarding left ventricular ejection fraction, global longitudinal strain, cardiac output, stroke volume, left ventricular end-diastolic volume, left ventricular end-systolic volume, E/A ratio, resting heart rate, peak heart rate, resting systolic blood pressure, and resting diastolic blood pressure. Also, there was no significant difference regarding any adverse events (AEs) (RR: 4.44 with 95% CI [0.47, 41.56], P = 0.19), AEs leading to withdrawal (RR: 2.87 with 95% CI [0.79, 10.43], P = 0.11), serious AEs (RR: 3.00 with 95% CI [0.14, 65.90], P = 0.49), or all-cause mortality (RR: 0.25 with 95% CI [0.03, 2.22], P = 0.21). Conclusion Exercise is associated with increased VO2 peak in cancer patients receiving cardiotoxic chemotherapy. However, there was no significant difference between exercise and usual care regarding the echocardiographic and safety outcomes.