In the present scenario where herbal and eco-friendly substances are being preferred over their synthetic counterparts, the present study is a contribution to the ongoing oncology research with a similar aim. Barringtonia acutangula L. and Stereospermum colais L. plants were selected based on their medicinal properties, which are well documented. The plants were subjected to a series of assays to evaluate its anti-cancer potentials. The preliminary screening by NO assay and MTT assay indicated the free radical scavenging and anti-cancer activity of the plants in the methanol and ethyl acetate extracts of S. colais and ethyl acetate extract of B. acutangula against Colon cancer cell lines Colo320. Further, DNA fragmentation assay attributed the cytotoxicity of the plant extracts to apoptosis. The CASPASE assays proved the activation of apoptosis in the cells treated with the plant extracts. Hence, it is suggested that both B. acutangula and S. colais have anti-cancer potentials. The present research suggests the use of these two medicinal plants as a therapeutic agent to treat the deadly disease of colorectal cancer.