Garcinia mangostana L. belongs to the Guttiferae family prominently seen in South Asia. Its fruits were frequently acknowledged as the “queen of fruits”. The Genus Garcinia comprises 35 genera and 240 species globally, among which 6 species were reported endemic to Western Ghats. The Pericarp and seed of G. mangostana are well known for their use in traditional systems of medicine against numerous ailments. In the current investigation, the hepatoprotective and antioxidant potential of methanolic extract of the pericarp of Garcinia mangostana L. were investigated against the acetaminophen-induced hepatotoxicity in HepG2 human liver cell lines. The qualitative analysis of methanol extract of Garcinia mangostana depicted the presence of immense phytoconstituents such as alkaloids, phenols, triterpenoids and flavonoids. It was observed that Garcinia mangostana acts as a potential hepatoprotective agent by reducing lipid peroxidation while significantly increasing the level of Glutathione (GSH) and superoxide dismutase (SOD) in dose-dependent manner. The hepatoprotective property of Garcinia mangostana was confirmed by the histopathological analysis and the results revealed that extract of G. mangostana recovered the liver cell lines towards almost normal level in a dose dependant manner from the histopathological alterations such as necrosis, vacuolation, etc., produced by acetaminophen.