Ethnopharmacological relevance Carpobrotus rossii (CR) has a history of use as a food and therapeutic agent by Australian indigenous peoples and early European settlers and is believed to contain a number of pharmacologically active polyphenolic compounds. Aims of the study Oxidation of low density lipoprotein (LDL), platelet aggregation, and inflammation contribute to the development and progression of atherosclerosis. The aim of the present study was to investigate the antioxidant, antiplatelet and anti-inflammatory activity of CR extract using human blood components. Materials and methods An assay employing in vitro copper-induced oxidation of serum lipids was used to assess antioxidant activity of CR extract (and tannin, flavonoid and pre- and post-flavonoid fractions). The effects of CR extract on ADP- and collagen-induced platelet aggregation, and on basal (unstimulated) and lipopolysaccharide (LPS)- and phytohaemagglutinin A (PHA)-stimulated cytokine release from peripheral blood mononuclear cells (PBMC) were also investigated. Results CR extract increased the lag time of serum oxidation (maximum of ~ 4-fold at 20 µg/ml) in a concentration-dependent manner. The antioxidant activity resided only in the tannin and post-flavonoid fractions. CR had no effect on ADP-induced platelet aggregation, but significantly decreased collagen-induced platelet aggregation. LPS, but not PHA, significantly increased the release of IL-1 and TNF- from PBMC. CR extract alone inhibited monocyte chemoattractant protein (MCP)-1 release and in the presence of LPS, inhibited IL-10, TNF and MCP-1 release compared to LPS alone. Conclusion CR has significant in vitro antioxidant, antiplatelet and, potentially, anti-inflammatory activity. Keywords: Carpobrotus rossii; antioxidant; lipid oxidation; platelet aggregation; cytokine release