Aphanamixis polystachya (Wall.) R.Parker, locally known as Pithraj, is a medicinal herb having enormous traditional applications. However, the scientific rationale underlying the ethnomedicinal claims was not well-founded. The current investigation aimed to explore the mechanistic insights of protective effects of ethanol extract of A. polystachya leaf (PT), given orally, on the chemical-intoxicated hepatic inflammation and fibrosis in Long-Evans female overiectomized rats. The GC-MS and HPLC-DAD analysis of PT revealed the presence of several bioactive metabolites, including polyphenolic compounds. Catechin hydrate, caffeic acid, syringic acid, epicatechin and p-coumaric acid have been identified and quantified in the ethanol extract of PT leaf. Intoxication with CCl₄ developed the oxidative stress, fibrosis and inflammation in liver of rats. Moreover, thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), advanced protein oxidation product (APOP) level were found increased; whereas superoxide dismutase (SOD) and catalase activities in the plasma and liver were decreased in CCl₄ administered rats. Treatment with PT prominently mitigated the oxidative stress (TBARS, NO, APOP), and inflammatory (MPO) markers and improved the endogenous antioxidant enzymes (catalase and SOD) activities in CCl₄-intoxicated rats. Additionally, histological assessment confirmed the clear manifestation of inflammation and fibrosis in the liver of CCl₄-intoxicated rats, which was prevented by PT and silymarin treatment. In conclusion, PT treatment may protect the liver in CCl₄-administered rats, probably by mitigating oxidative stress, inflammation and fibrosis, and also augmenting the function of the antioxidant enzymes.