Liver is a highly sensitive organ towards irradiation.This study aims to determine the potential repurposing effect of amlodipine (AML) (antihypertensive medicine)against acute hepatotoxicity induced by gamma radiation, using Silymarin (Sily) as a standardized hepatoprotective supplement in experimental rats. Thirty-two male rats were distributed into four groups: Control,Radiation (Rad),Rad+Sily, and Rad+AML. Following exposure to a single dose of gamma radiation (6Gy), rats received daily AML or Sily for a week. Results showed that administration of AML or Sily post gamma irradiation causes amelioration in the liver enzymes (AST, ALT) and the levels of total proteins and albumin,oxidative stress markers (NOx, MDA, GSH, ROS, XOand GST) and inflammatory markers (TNF-α, IL-6, and NF-κβ p65) also showed significantimprovement,when compared to the irradiated group. Additionally, AML ameliorates gamma irradiation-induced histological changes and alleviates the severity of hepatic injury thus histopathological finding supports the biochemical outcomes.It may be concluded that AML produces a hepatoprotectiveresponseaswell asSilymarin (a standardized hepatoprotectivesupplement) against gamma irradiation -induced acute liver injury in rats.