Abundant phenolic compounds, including rosmarinic acid (RA), caffeic acid, and their derivatives, are present in cold-pressed Perilla frutescens seed flour (CP-PFSF) after oil extraction. In this study, the in vitro antioxidant and hepatoprotective activities of the major phenolic components of CP-PFSF were assessed and compared. RA showed the highest antioxidant and hepatoprotectiveactivities. An RA-rich extract was prepared and its hepatoprotective effects were assessed in vitro and in vivo. In vitro, treatment with RA-rich extract markedly reduced H 2 O 2 -induced cytotoxicity, significantly prevented H 2 O 2 -induced lipid peroxidation and glutathione depletion, inhibited H 2 O 2induced apoptosis by regulating the expression of Bcl-2/Bax, caspase 9, and caspase 3, which are involved in the mitochondrial apoptosis pathway. In vivo, oral administration of RA-rich extract significantly reduced the levels of aspartate aminotransferase and alanine aminotransferase, and hepatocyte degeneration and neutrophilic infiltration induced by tert-butylhydroperoxide (t-BHP).