Medicinal plants are being used since ancient times in different tribes in India for numerous medicinal purposes. The essential facets of plant-based medicines, such as safety, quality, and efficiency, must be evaluated. Couroupita guianensis is a medicinally important plant, being used conventionally for curing varieties of medical ailments. From the safety point of view, limited information exists for the C. guianensis plant. Considering the facts mentioned above, this study evaluates the genotoxic potential of ethanolic leaf extract of C. guianensis, through an in vivo micronucleus test , which was conducted on mice (Strain: Hsd: ICR (CD1)). The main study consisted of three groups (5 male mice per group): vehicle control (corn oil), a treatment group (2000 mg/kg body weight), and positive control (Mitomycin-C, 1.0 mg/kg body weight). The methodology followed was the standard in vivo procedure as per the internationally approved OECD TG 474 guidelines with a two-day dosing schedule separated by 24 hours. Dose-volume used was 10 mL/kg body weight. Mice in each group exhibited normal behavior and were found clinically normal after dosing. Toxicity to bone marrow, as well as any statistically significant rise in the percent micronucleated polychromatic erythrocytes (% MNPCE), was not detected in mice that were treated with C. guianensis at 2000 mg/kg body weight when compared with the data of concurrent vehicle control. Statistically, a significant rise in the % MNPCE was obtained in mice treated with Mitomycin-C (1.0 mg/kg body weight), which confirmed the test system's suitability, the procedures, and efficiency of conditions employed in the test. Our study concluded that the plant is not showing any genotoxicity and can be used as a medicine to cure various reported ailments.