In recent days oxidative stress associates disease attains considerable importance in the developing countries like India due to constant change in life style and food habits. Free radical offers tireless quenching on the healthy tissue which in turn affects the entire physiology of the biological system. Siddha system of traditional medicine has wide range of formulations with the prospective anti-oxidant property and also having potential of curing several dreadful diseases. One such noble formulation is Seenakara parpam (SKP), Formulation like parpam presently used for clinical management of dysuria, blood stained dysentery, menorrhagia and other eye disorders. Still now there is no proper literature evidence claiming the antioxidant and hepatoprotective activity of the formulation SKP, hence this prompted us to pursue the preclinical investigation on exploring the efficacy of the drug SKP in selective animal model. The main aim of the present investigation is to evaluate the anti-oxidant and hepatoprotective activity of the formulation SKP against D-galactosamine induced oxidative stress in rats. Experimental rats were treated with test drug SKP at the dose of 200 and 400 mg/kg for the period of 21 days followed by this single I.P injection of D-galactosamine at the dose of 400 mg/kg to all the rats except control group. At the end of the study serum samples of collected and were analyzed for biochemical investigations including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TB), Total Protein (TP) and lactate dehydrogenase (LDH) level. Antioxidant profiling was carried out in liver tissue homogenate for the estimation of Lipid peroxidation (LPO), Superoxide dismutase (SOD), Catalase (CAT) and Glutathione peroxidase (GPx) level. Results of the study clearly indicates that there was a significant increase in (P<0 .01) serum AST, ALT, ALP, TB , LDH and LPO level further there was a significant decrease in (P<0.01) SOD, CAT, GPX and TP levels were observed in animals treated with D-galactosamine 400 mg/kg (Group II) as compared to normal control group (Group I). Pretreatment with SKP at the dose of 200 mg and 400 mg/kg to group IV and V and silymarin at the dose of 25 mg/kg to group III shown significant decrease in the levels of above indices like AST ,ALT, ALP, TB, LDH, LPO and increased level of SOD, CAT, GPX, TP in treated group. From the result of the present study it was concluded that the formulation SKP has promising antioxidant and hepatoprotective activity and it may be considered as drug of choice for the treatment of oxidative stress induced liver disease in future.