Background: Reactive oxygen species (ROS) contribute to increased intracellular oxidative stress, which has detrimental effects on normal cells and reduces antioxidant levels. This oxidative stress, particularly in the liver, causes inflammation, which leads to the development of acute and chronic liver diseases. Hence, substances with the ability to efficiently reduce ROS levels and oxidative stress are needed. Methods and Results: Kadsura coccinea stem extract exhibited a concentration dependent antioxidant activity and imporved alcohol dehydrogenase and aldehyde dehydrogenase effects. Noncytotoxic effects and increased cell activity were observed in HepG2 cells treated with K. coccinea stem extract under conditions of hydrogen peroxide induced hepatotoxicity. Additionally, the extract effectively reduced ROS levels, as confirmed by 2′,7′-dichlorodihydrofluorescein diacetate (DCFHDA) assay in HepG2 cells simultaneously exposed to hydrogen peroxide and the K. coccinea stem extract. mRNA expression analysis revealed elevated levels of antioxidant enzymes, including superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPx1), and catalase (CAT). Conclusions: These findings reveal the potential therapeutic value of K. coccinea stem extract for oxidative stress related liver disorders.Kadsura coccinea;Antioxidant;Ethanol Extract;Hepatoprotective Effects;Reactive Oxygen Species