Annona squamosa, Datura metel, and Mentha piperita are extensively used in traditional medicine. These were reported to have several medicinal properties. However, these plants are also reported to be toxic to some cell types. Human peripheral blood lymphocytes were treated with various concentrations of aqueous leaf extracts of all three plants to assess the toxic effects on the cells. Toxicity studies were performed by the Trypan Blue dye exclusion method. Decrease in viability percentage was noticed with increasing concentration of plant extracts in the cell culture system. Cell morphology was then studied using Giemsa staining and fluorescent microscope using Acridine Orange and Ethidium Bromide staining and a significant increase in the apoptotic features were noticed in cells treated with the plant extracts. The apoptotic cell morphology has been evaluated by fluorescent microscopy. It was observed that exposure to increasing concentrations of crude plant extract (50 μg/ml, 100 μg/mL, and 150 μg/mL) resulted in a concentration dependent decrease in cell viability. Among the 03 medicinal plants studied in the present work, lymphocytes treated with Annona squamosa extract showed highest cytotoxic and apoptotic activity.