Indiscriminate bioaccumulation of heavy metals in body have been linked to oxidative stress arising from peroxidation of membrane of biomolecules which consequently manifest as neurologic, hepatic, renal and cardiovascular disorders. Therefore this study is sought to investigate the protective and inhibitory effect of Solanum indicum leaf extract against lead acetate induced lipid peroxidation and hepatomegaly in liver of albino rats. Results showed that incubation of liver homogenate with the pro-oxidant (Pb 2+) caused significant (P<0.05) increase in levels of thiobarbituric reactive substances (TBARS), while the extract offered highly significant (P<0.05) dose dependent inhibitory potential against the increase in TBARS induced by the pro-oxidant. Besides, results showed that treatment of rats in vivo with the respective doses of the extract significantly altered and attenuated serum and liver levels of biomarker enzymes (AST, ALT and ALP) in group C animals compared to rats in group B fed with lead acetate only that demonstrated significant (P<0.05) increase in enzyme activity while control group A received no treatment. Hence, the results suggest that Solanum indicum extract could confer protection on the liver tissues against oxidative stress and hepatomegaly and the extract may not be toxic at the doses investigated.