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<i>Vernonia amygdalina</i> (<i>V. amygdalina</i>) leaves are commonly used in traditional medicine around the world for the treatment of a plethora disorders, including heart disease. The aim of this study was to examine and evaluate the cardiac effect of <i>V. amygdalina</i> leaf extracts using mouse induced pluripotent stem cells (miPSCs) and their cardiomyocytes’ (CMs) derivatives. We used a well-established stem cell culture to assess the effect of <i>V. amygdalina</i> extract on miPSC proliferation, EB formation and the beating activity of miPS cell-derived CMs. To study the cytotoxic effect of our extract, undifferentiating miPSCs were exposed to different concentrations of <i>V. amygdalina</i>. Cell colony formation and EB morphology were assessed using microscopy, whereas the cell viability was accessed with an impedance-based method and immunocytochemistry following treatment with different concentrations of <i>V. amygdalina</i>. Ethanolic extract of <i>V. amygdalina</i> induced toxicity in miPSCs, as revealed by a decrease in cell proliferation and colony formation, and an increase in cell death at a concentration of ≥20 mg/mL. At a concentration of 10 mg/mL, the rate of beating EBs was observed with no significant difference regarding the yield of cardiac cells. In addition, <i>V. amygdalina</i> did not affect the sarcomeric organization, but induced positive or negative effects on miPS cell-derived CMs’ differentiation in a concentration-dependent manner. Taken together, our findings demonstrate that the ethanolic extract of <i>V. amygdalina</i> affected cell proliferation, colony forming and cardiac beating capacities in a concentration-dependent manner.