Background: Caesalpinia bonduc (CB) is said to own various pharmacological and therapeutic application against a number of diseases. It is used widely in folk medicine to treat liver diseases. In the present study, we have made a sincere effort to evaluate the hepatoprotective activity of CB leaf extracts against Paracetamol (PCM) induced toxicity and their mechanism of hepatoprotection in the human Hepatocarcinoma cells (HepG2 cells) thereby providing scientific evidence for the same. Material and Methods: The hepatoprotective activity of CB was assessed in-vitro by the estimation of glutathione (GSH) and Malondialdehyde (MDA), anti-apoptotic assay/Annexin V and the expressions of genes such as Glutathione Reductase (GS-R) and Glutamate-Cysteine Ligase, Catalytic (GCLC). Results: The obtained results suggest that the aqueous extract of CB possess significant hepatoprotective activity. This activity may be due to the possible antioxidant property and the free radical scavenging ability of the extracts, which might clear the toxic metabolites of PCM. Conclusion: The present study suggests that the aqueous extract of CB have potential hepatoprotective activity, which may prevent the lipid peroxidation of the cell membrane by its antioxidant properties.