The aim of this study was to elucidate the protective ability of the Perilla frutescens cv. Chookyoupjaso mutant water extract (PFWE) against oxidative injury in vitro and in vivo. In in vitro experiments, our results showed that PFWE indicated the intracellular reactive oxygen species (ROS) scavenging activity as well as cytoprotective effect in SIN-1-treated HepG2 cells. The intracellular ROS scavenging activity of PFWE was 44% at 50 ${mu}g/mL$, 50% at 100 ${mu}g/mL$, and 56% at 200 ${mu}g/mL$. Furthermore, in vivo results showed that treatment with PFWE attenuated the activity of serum alkaline phosphatase (ALP) and lipid peroxidation increased by carbon tetrachloride ($CCl_4$) and also markedly recovered the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) decreased by $CCl_4$ in BALB/c mice. GPx activity was elevated almost 3-fold compared to control group at 50 mg/kg of PFWE. The present study suggests that PFWE possesses significant protective effects against oxidative injury.