Background <p>Myocardial ischemia-reperfusion injury (MIRI) markedly impairs cardiac functional recovery and represents a major determinant of adverse outcomes in patients with ischemic heart disease. Ginsenosides, the principal bioactive constituents of ginseng, exert significant cardioprotection against MIRI. This review systematically summarizes and analyzes in vivo (animal) studies to clarify the efficacy and underlying mechanisms of ginsenosides in MIRI.</p> Methods <p>The PubMed, EMbase, Web of Science, Cochrane Library, CNKI, WanFang, and Cqvip databases were systematically searched from inception to 31 July 2024. In vivo studies evaluating ginsenosides pretreatment or post-treatment in models of MIRI were identified. Outcome measures comprised myocardial infarct size and indices of hemodynamic performance, myocardial injury, apoptosis, inflammation, and oxidative stress. A meta-analysis was conducted with RevMan 5.4 and Stata/MP 14.0.</p> Results <p>Thirty-four eligible articles encompassing 505 experimental animals were included. Funnel plots, Egger’s tests, and sensitivity analyses confirmed the robustness of the findings. Compared with controls, ginsenosides treatment significantly reduced myocardial infarct size and improved hemodynamic indices (P &lt; 0.0001). Ginsenosides also attenuated MIRI-induced elevations of lactate dehydrogenase, creatine kinase-MB, creatine kinase, malondialdehyde, tumor necrosis factor-α, interleukin-6, interleukin-1β, and cardiomyocyte apoptosis (P &lt; 0.0001). Subgroup analysis further revealed that pre-ischemic ginsenosides administration conferred greater protection than post-reperfusion treatment.</p> Conclusion <p>Ginsenosides play a significant role in the prevention and treatment of MIRI. Ginsenosides can reduce the area of myocardial infarction and improve myocardial damage through anti-inflammatory, antioxidative stress, anti-apoptosis, regulation of autophagy, and energy metabolism.</p>