Traditional medicine plays a crucial role in healthcare and disease management in African communities; however, the quality and toxicity of these remedies remain largely unknown, particularly concerning the chronic conditions that are managed by traditional medicines. Despite the widespread use of Kigelia africana as a traditional medicine for chronic conditions, its genotoxic and mutagenic effects remain unclear. This study aimed to address this knowledge gap by examining the genotoxic and mutagenic properties of aqueous and ethyl acetate crude extracts of Kigelia africana fruits obtained from the Kazungula District of Zambia. The study used quantitative fluorescence microscopy to determine mutagenicity and genotoxicity and compared the results with the Ames results obtained in this study. The study found that the aqueous extract had no effect on cell viability, while the ethyl acetate extract caused a dose-dependent reduction in cell viability. The effects of the fruit extracts on His+ revertants were comparable to those of the negative control, showing no mutagenic effects. The study also found that the average nuclear area of Vero cells increased significantly with the highest concentration of the ethyl acetate fruit extract, but there was no significant effect on the multi+dual/mononucleated Vero cell ratio following a 48-hour exposure. This study demonstrated for the first time that K. africana fruit extracts are not cytotoxic and do not have mutagenic potential and that the extracts do not exhibit genotoxic effects at therapeutic doses.