In this study, the antioxidant activities of 21 species of marine algae were assessed via an ABTS free radical scavenging assay. The Ishige okamurae extract tested herein evidenced profound free radical scavenging activity, compared to that exhibited by other marine algae extracts. Thus, I. okamurae was selected for use in further experiments, and was partitioned with different organic solvents. Profound radical scavenging activity was detected in the ethyl acetate fraction, and the active compound was identified as the carmalol derivative, diphlorethohydroxycarmalol, which evidenced higher levels of activity than that of commercial antioxidants. Moreover, the protective effects of diphlorethohydroxycarmalol against H2O2-induced cell damage were evaluated. Intracellular reactive oxygen species (ROS) were overproduced as the result of the addition of H2O2, but this ROS generation was reduced significantly after diphlorethohydroxycarmalol treatment; this corresponds to a significant enhancement of cell viability against H2O2-induced oxidative damage. The inhibitory effects of diphlorethohydroxycarmalol against cell damage were determined via comet assay and Hoechst staining assay, and diphlorethohydroxycarmalol Was found to exert a positive dose-dependent effect. These results clearly indicate that the diphlorethohydroxycarmalol isolated from I. okamurae exerts profound antioxidant effects against H2O2-mediated cell damage, and treatment with this compound may be a potential therapeutic modality for the treatment or prevention of several diseases associated with oxidative stress. Crown Copyright (C) 2008 Published by Elsevier Ltd. All rights reserved.