The antioxidant properties of the red seaweed Callophyllis japonica were investigated. An ethanol extract isolated from C. japonica exhibited intracellular reactive oxygen species, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and lipid peroxidation inhibitory activity. The radical scavenging activity of the extract protected the viability of Chinese hamster lung fibroblast (V79-4) cells exposed to H2O2. Furthermore, the extract reduced the proportion of apoptotic cells induced by H2O2, as demonstrated by decreased sub-G1 hypo-diploid cells and decreased apoptotic body formation. The extract also increased the activities of the cellular antioxidant enzymes, superoxide dismutase and catalase. Together, these findings suggest that C. japonica exhibits antioxidant properties.