Abstract : Plants are rich in natural products with medicinal value, which have served as the foundation for numerous pharmaceutical drugs. Plants traditionally ingested may have various biological effects, including anticancer activity. This study involves assessing traditional South African plants for anticancer properties. Organic and aqueous extracts were prepared from Bulbine narcissifolia. These plants were assessed for cytotoxicity and caspase-3 activation in a melanoma cell line in vitro (A549). The cells were grown in DMEM media with foetal bovine serum and incubated at 37°C in a humidified atmosphere of 5% CO2. The cytotoxicity results of the studied plant extracts revealed that all extracts displayed selective activity towards the cancer cell line, with methanolic root extracts of Bulbine narcissifolia and O. sinuatum exhibiting high cytotoxicity activity, with IC50 values of 61.93 and 74.92 µg/mL, respectively. The other extracts, B. narcissifolia and O. sinuatum aqueous root extract, inhibited cell growth with IC50 values of 100.1 and 126.9 µg/mL, respectively higher then methanolic extract. Methanol and aqueous extracts were tested on A549 cancer cells to confirm their cytotoxic effects. Treated cells showed reduced cell numbers, intracellular spaces, and signs of apoptosis like cell shrinkage and membrane blebbing, while untreated cells had a normal morphology with more cells and no intracellular spaces. These findings imply that Bulbine narcissifoliaand O. sinuatum are promising sources of valuable natural substances with the potential for developing novel anticancer drugs.