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Objective: The present study was carried out to evaluate the in vitro hepato protective activity of unexploited plants, Sphaeranthus amaranthoides and Oldenlandia umbellate on CCl 4 induced liver injury, which are indigenous to South India. Methods: in the present study the methanolic extracts from Sphaeranthus amaranthoides and Oldenlandia umbellata were studied against the carbon tetrachloride hepatotoxicity. Results: significant hepatoprotective effect was obtained against carbon tetrachloride induced liver damage as judged from serum marker enzyme activities (SGOT, SGPT, ALT, and TB) and a normal architecture of liver compare to toxic control. Conclusion: the result revealed that methanolic extracts of Sphaeranthus amaranthoides and Oldenlandia umbellata could be useful in preventing CCl 4 induced liver injury.