Limnophila heterophylla, a medicinal plant native to tropical and subtropical South and Southeast Asia (Indomalaya), including southern China and it is commonly used in folk medicine to treat various diseases. The aim of the present study was to evaluate the hepatoprotective and in-vivo antioxidant activities of Limnophila heterophylla. The hepatoprotective activity of methanol extract of leaves of Limnophila heterophylla was evaluated against carbon tetrachloride + olive oil (1:1) induced hepatic damage in rats. The methanol extract of leaves of Limnophila heterophylla at dose of 250 and 500 mg/kg were administered orally once daily for seven days. Serum enzymatic levels of serum glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase (SALP), Lactate dehydrogenase (LDH), total bilirubin (TB), and total protein (TP) were estimated. In-vivo antioxidant activity of methanol extract of Limnophila heterophylla was evaluated by various assays including superoxidedismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GRD), reduced glutathione, and malondialdehyde (MDA) levels in liver tissues. The results of the carbon tetrachloride -induced liver toxicity experiments showed that rats treated with the methanol extract of Limnophila heterophylla 500 mg/kg showed a significant decrease in SGOT, SGPT, ALP, LDH, and TB levels, which were all elevated in the CCl4 + olive oil group (p < 0.01). Limnophila heterophylla leves extracts therapy also protective effects against histopathological alterations. The extract showed potent activities on SOD, CAT, GRD, GPx, reduced glutathione and MDA levels. Further histopathological examination of the liver sections was carried out to support the induction of hepatotoxicity and hepatoprotective efficacy. The results of the present study strongly reveal that methanol extract of leaves of Limnophila heterophylla had hepatoprotective and antioxidant activities against carbon tetrachloride - induced hepatic damage in experimental animals.