Trilobatin is a dihydrochalcone glucoside and derivative of phloretin that has been found in Rooibos (A. linearis) tea and has diverse biological activities. It reduces survival of Bel 7402 and HepG2 cancer cells when used at a concentration of 100 μM. Trilobatin increases superoxide dismutase (SOD) and glutathione peroxidase (GPX) activity (EC50s = 129 and 128 μM, respectively) and inhibits lipid peroxidation (IC50 = 88 μM) in rat liver homogenates. Pretreatment with trilobatin reduces hydrogen peroxide-induced cell death and production of mitochondrial reactive oxygen species (ROS), prevents reduction in the mitochondrial membrane potential, and increases the activity of GPX, SOD2, and isocitrate dehydrogenase 2 (IDH2) in PC12 neuronal cells. Trilobatin inhibits infection by various HIV-1 strains (IC50s = 2.91-27.11 μM) without inducing cytotoxicity in target cells.