Abstract Cyphomandra betacea Sendt. (tamarillo) is a subtropical fruit containing rich contents of anthocyanins and carotenoids. The antioxidant activity was investigated using a crude ethanol extract of C. betacea fruit and its partitioned fractions, i.e. the ethyl acetate, butanol and water fractions. The ethyl acetate fraction exhibited the highest DPPH scavenging activity, Trolox equivalent antioxidant capacity (TEAC) and total phenol content. C. betacea phenolics in ethyl acetate fraction inhibited copper-induced LDL oxidation equally to or more effectively than dl -α-tocopherol, as measured by decreased formation of thiobarbituric acid-reactive substances (TBARS), conjugated diene and relative electrophoretic mobility (REM). Furthermore, 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) reduction assay showed that C. betacea phenolics in ethyl acetate fraction prevent oxidative stress-induced cell death in neuronal PC12 cells in a dose-dependent manner via attenuation of ROS production. In conclusion, C. betacea phenolics are potent antioxidants which can inhibit LDL oxidation in vitro and ROS production in PC12 cells.