Background: Holarrhena antidysenterica L. traditionally treats amoebic dysentery, diarrhoea, asthma, bronchopneumonia, malaria and some other disorders. Aim: The current study was designed to explore the effects and possible mechanisms of Holarrhena antidysenterica on paracetamol induced hepatic damage in a rat model. Materials and methods: The Hepatic damage was induced in male wistar rats with PCM (2g kg-1) administration for 4 weeks. Liver histopathological study was performed, and the liver function was performed by determining the (SGPT) Serum glutamate pyruvate transaminase, (SGOT) Serum glutamic oxaloacetic transaminase, Alkaline phosphatase (ALP) and Total bilirubin (TB) for evaluating the effect of HAE on hepatic damage. The possible mechanisms were investigated by measuring hepatic collagen metabolism and oxidative stress level. Findings: HA extract care significantly inhibited the loss of liver weight induced by PCM. Then the HAE improved the liver function of rats as recorded by decreased serum enzymatic activities of SGPT, SGOT ALP and TB (p<0.05, p<0.01). Histopathological results indicated that HAE alleviated liver damage and reduced the formation of fibrous septa. Moreover, HAE significantly decreased liver Hydroxyproline (Hyp) content. It also decreased liver Malondialdehyde concentration, increased activities of liver superoxide dismutase, catalase, and glutathione peroxidase. The hematological Parameter induced by HAE is normal compared with the control. The standardized extract HPTLC investigation uncovered the presence of some critical phenolic compound. Conclusion: This examination demonstrated that Holarrhena antidysenterica could be taken as a decent common wellspring of the hepatoprotective agent.