Despite regular exercise benefits, acute exhaustive exercise elicits oxidative damage in liver. The present study determined the hepatoprotective properties of ginsenoside-Rg1 against exhaustive exercise-induced oxidative stress in rats. Forty rats were assigned into vehicle and ginsenoside-Rg1 groups (0.1 mg/kg bodyweight). After 10-week treatment, ten rats from each group performed exhaustive swimming. Estimated oxidative damage markers, including thiobarbituric acid reactive substance (TBARS) (67%) and protein carbonyls (56%), were significantly (P < 0.01) elevated after exhaustive exercise but alleviated in ginsenoside-Rg1 pretreated rats. Furthermore, exhaustive exercise drastically decreased glutathione (GSH) content (∼79%) with concurrent decreased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities. However, these changes were attenuated in Rg1 group. Additionally, increased xanthine oxidase (XO) activity and nitric oxide (NO) levels after exercise were also inhibited by Rg1 pretreatment. For the first time, our findings provide strong evidence that ginsenoside-Rg1 can protect the liver against exhaustive exercise-induced oxidative damage.