Cancer is one of the leading causes of death both in developed and developing countries and was responsible for the loss of 9.6 million lives in 2018 alone. Development of drug resistant strains of cancer has hampered cancer therapy. Worldwide, plants have been reported to play a major role in the traditional treatment of cancer. Irinotecan, paclitaxel, and vincristine are some of the examples of plant derived compounds that are used as anticancer agents. This study evaluated the cytotoxicity, anti-inflammatory, and antioxidant activities of Pittosporum viridiflorum Sims and Hypoxis colchicifolia Baker, two plants used in South African traditional medicine for treating cancer. Acetone, ethanol, and water (hot and cold) extracts were screened against four human cancer lines (breast MCF-7, colorectal Caco-2, lung A549 and cervical Hela) for anticancer potential. Two normal cells; Vero monkey kidney and bovine dermis were used to test for cytotoxicity, and Salmonella typhimurium TA98 and TA100 were used to determine genotoxicity of the samples. The acetone extract of P. viridiflorum had significant cytotoxicity against the cancer cells (MCF7, Caco-2, A549 and Hela) with LC50 values ranging from 3.16–26.87 μg/ml. The same extract had noteworthy anti-inflammatory activity against 15-lipoxygenase with IC50 value = 5.01 μg/ml and was not toxic against Vero and bovine dermis cells nor was it genotoxic. This warrants further extensive study to determine the mechanism of action of anticancer and anti-inflammatory activities as well as to identify specific compounds responsible for the observed activities.