The Opuntia spp. have been used in traditional medicine for many centuries. It is used in the management of diseases that involves oxidative stress, especially diabetes, obesity and cancer. Opuntia stricta (Haw) is one of the relatively unknown species in South Africa where it is regarded more as a weed. Because of this, not much is known about its chemical composition. To determine the chemical composition, antioxidant, anti-inflammatory, and cytotoxic activities of Opuntia stricta cladodes. The phytochemical composition of acetone, aqueous and ethanol extract of cladodes of Opuntia stricta (Haw), as well as the vitamins A, C and E of its dried weight cladodes and the antioxidant activities, were evaluated using standard in vitro methods. The anti-inflammatory and cytotoxic activities were evaluated using cell-based assays. The phytochemical composition and vitamins were determined spectrophotometrically, while the antioxidant activities were determined by DPPH, nitric oxide, hydrogen peroxide scavenging activity and phosphomolybdenum (total) antioxidant activity. Anti-inflammatory activity was determined using RAW 264.7 cells, while cytotoxicity was determined using U937 cells. The phytochemical composition showed a significant difference in the various extracts. The total phenolics were higher than other phytochemicals in all the extracts used. All the extracts displayed antioxidant activity, while most of the extracts showed anti-inflammatory activity. Only one extract showed cytotoxicity, and it was mild. The results show that the Opuntia stricta is rich in polyphenolic compounds and has good antioxidant activity as well as anti-inflammatory activities.