Objectives: This study was performed to investigate the effect of Jaeumgeonbigagamtang (JGT) onrestraint-induced oxidative stress in the mouse brain. Methods: After treatment with JGT, CBC, ROS, MDA, TAC, SOD, activity of catalase, and total GSH content were analyzed. Results: JGT had a strong antioxidant activity by in vitro assay as presented GEAC. JGT treatment significantly ameliorated decrease of blood WBC and increase of platelet count. JGT (50mg/kg) treatment significantly ameliorated increase of MDA and GSH content level in brain tissue. JGT (100mg/kg) treatment significantly ameliorated increase of MDA and activity of TAC level in brain tissue. JGT (200mg/kg) treatment significantly ameliorated increase of ROS, MDA, activity of TAC level and depletion of catalase level in brain tissue. Conclusion: The present study demonstrated antioxidant activity in brain tissue. This result would be consistent with the long clinical efficacy of JGT, and this finding may provide a strong possibility of JGT as a drug candidate for brain-specific multiple disorders and symptoms.