The present book presented the various models of hepatoprotective screening as well as a study aimed at describing the investigation of the antioxidant and hepatoprotective activity of methanolic flower extract of Nerium oleander. In vitro antioxidant activity MENO-F was evaluated by various assays, including reducing power, lipid peroxidation, DPPH, ABTS, superoxide anion, hydroxyl radicals and metal chelation. The hepatoprotective and in vivo antioxidant activity of MENO-F were evaluated against CCl4-induced hepatic damage in rats. The extract showed potent activities on reducing power, lipid peroxide, DPPH, ABTS, superoxide anion, hydroxyl radical and metal chelation. The substantially elevated serum enzymatic levels of AST, ALT, ALP and total bilirubin were found to be restored towards normalization significantly by the MENO-F in a dose dependent manner with maximum hepatoprotection at 400 mg/kg dose level. The histopathological observations supported the biochemical evidences of hepatoprotection. Elevated level of superoxide dismutase (SOD) and decreased level of malondialdehyde (MDA) further strengthen the hepatoprotective observations.