Traditional Chinese medicine (TCM) is an attractive model for studying antioxidant-based composite therapy. We previously reported that Shengmai San (SMS), a TCM formulation for treating cardiac disorders, inhibited cerebral oxidative damage in rats when evaluated by both glutathione peroxidase (GPX) activity loss and thiobarbituric acid reactive substance (TBARS) formation after forebrain ischemia-reperfusion. In the present study, we further examined the preventive effect of SMS and related decoctions composed of three component herbs (Panax ginseng, Ophiopogon japonicus and Schisandra chinensis) against oxidative brain injury to rationalize the complex formulation of SMS. Schisandra chinensis itself and decoctions containing it all inhibited TBARS formation in vivo. In contrast, Ophiopogon japonicus itself and formulations containing it had little effect on TBARS formation. GPX activity loss in vivo, on the other hand, was completely prevented only by SMS and Ophiopogon japonicus itself. A comparison of the in vitro antioxidant potential of SMS and related decoctions and in vivo effectiveness in preventing cerebral oxidative damage revealed that all the in vitro antioxidant indices examined here essentially correlated well with inhibition of TBARS formation in vivo. DPPH quenching and crocin bleaching activities showed particularly good correlation, and then, superoxide scavenging activity followed. However, none of them correlated with the inhibition of GPX activity loss in vivo. The role of each component herb is also discussed for the SMS effect.