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Objective The objective of this study was to assess the in vitro hepatoprotective activity of Clerodendrum japonicum leaves. Methods Clerodendrum japonicum leaves were subjected to extraction process followed by phytochemical studies. The obtained extracts were studied to assess the cytotoxicity and in vitro hepatoprotective activity using HepG2 cell line culture. Results The phytochemical analysis of Clerodendrum japonicum leaves signaled the presence of phytosterols terpenoids phenolics tannins flavonoids carbohydrates and saponins. The alcoholic extract showed 38.50 cell growth inhibition indicating lower cytotoxicity of alcoholic extract compared to the other extracts and also 35.99 of protective effect in HepG2 cells against paracetamol induced toxicity in comparison to Silymarin as the standard drug. Conclusion The present study suggests that the ethanolic extract of Clerodendrum japonicum leaves can be useful as a hepatoprotective agent.nbsp