Aim: Statins have been suggested as potential agents for mitigating chemotherapy-induced cardiotoxicity, particularly in the context of anthracyclines and/or trastuzumab treatment. However, conflicting findings have emerged from randomized controlled trials (RCTs) and observational studies. Therefore, the primary objective of this study is to comprehensively investigate the effectiveness of statins in ameliorating chemotherapy-induced cardiotoxicity in the case of anthracyclines and/or trastuzumab. Methods: We conducted a systematic search in major databases, including PubMed, Scopus, Web of Science, and Cochrane, up to May 10, 2023. Our main outcomes were the risk ratio (RR) of cardiotoxicity and the mean difference (MD) in left ventricular ejection fraction (LVEF%). We performed Trial Sequential Analysis (TSA). Results: A total of 9 studies (6 observational and 3 RCTs) were included. Although the pooled results from all studies favored statins in the incidence of cardiotoxicity (RR 0.54, 95% CI [0.37, 0.79]), evidence from RCTs only (n = 2) did not indicate any significant change in risk (RR 0.50, 95% CI [0.17, 1.45]). Similarly, while the overall change in LVEF% was significant when pooling all studies (MD 4.38, 95% CI [0.41, 8.35]), RCTs only (n = 3) showed no significant change (MD 3.94, 95% CI [-1.07, 8.96]). The TSA curve for RCTs evaluating LVEF% did not cross the conventional boundary for statistical significance, indicating that the cumulative evidence did not reach the predefined level of statistical significance threshold, with no strong evidence to establish a statistically significant relationship. Conclusion: The effectiveness of statins in mitigating chemotherapy-induced cardiotoxicity remains inconclusive, and the current evidence from randomized controlled trials does not demonstrate significant associations. Further research is necessary to clarify the role of statins in chemotherapy-induced cardiotoxicity.