The objective of this study was to find out any alternative natural product to address the hepatic problems. Though many medicinal plants have been reported for hepatoprotective potential but still there is a need to explore further their medicinal effect on scientific basis. Hepatoprotective potential of selected medicinal plants (Silybum marianum, Artemisia absinthium and Rheum emodi) in different combinations against paracetamol induced liver damage was studied. The phytochemical constituents of selected medicinal plants in combinations were tested by measuring total phenolic content (276.26 to 356.57 GAE) and total flavonoid content (13.01 to 25.63 CE). The antioxidant activity of selected medicinal plants in combination was evaluated through DPPH (76.81 to 92.33 % inhibition) and reducing power in term of absorbance (0.964 to 1.652). The antioxidant effect of medicinal plants at cellular level was further explored using H2O2 induced DNA damage on pUC19 plasmid DNA. It was found that the protective effect of plants extracts was concentration dependent. The safety of medicinal plants was evaluated through various toxicological assays including hemolytic, brine shrimp lethality and mutagenicity. The cytotoxicity findings showed that the plants are safe and may be used as medicine. Biochemical profiling of selected medicinal plants was performed through liquid chromatography mass spectrometry (LCMS). The hepatotoxin, paracetamol significantly increased the levels of SGPT, SGOT and ALP whereas the levels of protein and albumin were decreased. The combination containing silymarin extracted from S. marianum, aqueous mixture of both A. absinthium and R. emodi were given to experimental animals with different doses. The hepatoprotective effect was evaluated by studying various biochemical parameters (SGPT, SGOT, ALP, Protein and Albumin). The administration of medicinal plants in various combinations altered the biochemical markers and exhibited significant hepatoprotective activity. The experimental animals were slaughtered at the end of study. The levels of antioxidant enzymes, superoxide dismutase, glutathione peroxidase and catalase were decreased in positive control group (paracetamol treated). The levels of antioxidants enzymes in medicinal plants treated groups remained in normal limit as in the control group. Histopathological examination of liver tissues of control and treated animals showed significant difference indicating that the combinations of selected medicinal plants successfully restored the liver functions. Although majority of the combinations restored the liver functions but the most suitable combination was the least quantity i.e. 100 mg of each plant. It is concluded that the medicinal plants in combination used in this study is an effective and promising formulation against paracetamol induced liver damage.