To evaluate the antioxidant status of ethanolic extract of Solanum villosum leaves (EESVL) using mammalian liver slice technique in in vivo simulated in vitro model. Antioxidant activity of Solanum villosum was studied against H2O2 induced free radicals in goat liver. Administration of H2O2 showed significant decline in the levels of antioxidant enzymes in liver homogenate. Pretreatment with Solanum villosum leaf extract had significant protection in those levels within normal range. Also the plant normalized the lipid peroxidation which evidently showed that the ethanol extract of Solanum villosum had a potent antilipid peroxidative effect. The present study suggests that Solanum villosum had a potent antioxidant effect and it can be used to treat various diseases caused by free radicals.