Liver ailment is one of the severe health issues all over the sphere. Hepatic damage or failure due to consumption and breathing of hepatotoxin is increasing worldwide. Rifampicin high dosage can cause severe injury to the liver. Today publics wish herbal drugs due to its high efficiency and absence of side effects. Herbal medicines are available for each and every disorder ranging from diabetes to rejuvenators. These facts promoted us to select a medicinal plant Glinus lotoides for the present study which is known as ‘Siruserupadai’ in Tamil. Amid the later ponder, ethanolic extricate was chosen for the anti-hepatotoxicity action; it has maximum numbers of phytoconstituents (Glycosides, saponins, proteins, alkaloids, and flavanoids). Five groups of animals were taken for the test named as control, rifampicin treated group, Silymarin treated group (10 mg/Kg), Ethanolic Extract of Glinus lotoides Linn. (EEGL) treated group (200 mg/Kg), EEGL treated group 400 mg/kg. Rifampicin effectively and particularly ties to RNA polymerase; it represses the amalgamation of all shapes of RNA. It induces fatty liver and finally cirrhosis which is exited by increment the action of serum biological catalysts like SGPT, SGOT and alkaline phosphatase. The hepatoprotective activities was appeared by bringing down the serum biochemical parameters (enzymes and bilirubin) within the rifampicin inebriated rats pre-treated with ethanolic extricate at 200 and 400 mg/kg. The prophylactic impact is reasonably comparable to that of Silymarin, suggesting the EEGL can be potential source of hepatoprotectives.