Solanum xanthocarpum Schard. and Wendl. (Solanaceae) has been used in traditional Indian medicines for its antioxidant, anti-inflammatory, and antiasthmatic properties. The present study demonstrates the antioxidant and hepatoprotective effects of S. xanthocarpum. On the basis of in vitro antioxidant properties, the active fraction from column chromatography of the methanol extract of S. xanthocarpum leaves (SXAF) was chosen as the potent fraction and used for hepatoprotective studies in rats. The antioxidant activity was evaluated by 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and reducing power assays. Rats were pre-treated with 100 and 200 mg/kg b.w. of SXAF for 14 d with a single dose of CCl4 in the last day. Hepatoprotective properties were determined by serum biochemical enzymes, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), antioxidant enzymes (SOD, CAT, GSH, and GST), and histopathology studies. SXAF exhibited significant antioxidant activity in scavenging free radicals with IC50 values of 11.72 µg (DPPH) and 17.99 µg (ABTS). Rats pre-treated with SXAF demonstrated significantly reduced levels of serum LDH (1.7-fold), ALP (1.6-fold), and AST (1.8-fold). Similarly, multiple dose SXAF administration at 200 mg/kg b.w. demonstrated significantly enhanced levels of SOD (1.78 ± 0.13), CAT (34.63 ± 1.98), GST (231.64 ± 14.28), and GSH (8.23 ± 0.48) in liver homogenates. Histopathological examination showed lowered liver damage in SXAF-treated groups. These results demonstrate that SXAF possesses potent antioxidant properties as well as hepatoprotective effects against CCl4-induced hepatotoxicity.