Species of Allamanda and Plumeria have been used as medicinal plants for a long time. This study investigates the cytotoxicity and genotoxicity of their extracts on lymphocytes and HeLa cells using cell viability tests and comet assay. A. cathartica, A. violacea, P. obtusa, and P. rubra were collected and hexane-extracted. The maximum concentrations of crude extracts were 315, 625, 357, and 303 mg/ml, respectively. For cytotoxicity on lymphocytes treated with the maximum final concentration of the four extracts, the cell viabilities were 79%, 96%, 70%, and 60%, respectively. In HeLa cells, the IC 50 was 13.5, 3.75, 21.5, and 14.5 mg/ml, respectively. These extracts showed significant genotoxicity (p < 0.01) on both lymphocytes and HeLa cells. These findings suggest that Allamanda and Plumeria should not be used as medicinal plants.