Context: Habb-e-Asgand, a polyherbal Homeopathy/Unani drug from Hamdard Wakf Laboratory, India, used in arthritis, gout and joint pain, is a mixture of many herbal medicinal plants. Scientific attempts to test and validate its efficacy are meager. Objective: To evaluate the hepatoprotective and antioxidative potential of Habb-e-Asgand against paracetamol toxicity. Materials and methods: Swiss albino male mice (n = 5/group) were treated with Habb-e-Asgand (250 mg/kg, body weight (b.w.) in normal saline orally for 14 days followed by a single dose of paracetamol (400 mg/kg b.w./normal saline) intraperitoneally 24 h before euthanization. We estimated liver function (LFTs) using diagnostic kits, while antioxidant enzymes, cytochrome P450 (CYP) and lipid peroxidation (LPO) were measured using spectrophotometric methods. Results: Paracetamol alone induced LFTs enzymes significantly (p<0.05 and p<0.01, 0.001), serum glutamate pyruvate transaminase (SGPT, similar to 70%), serum glutamate oxaloacetate transaminase (SGOT, similar to 20%), alkaline phosphatase (ALP, similar to 20%), total bilirubin (similar to 30%), CYP activity (similar to 50%) and LPO (similar to 45%), while it significantly inhibited the activity of antioxidant enzymes glutathione reductase (GR, similar to 35%), glutathione peroxidase (GPx, similar to 40%), glutathione S-tranferase (GST, similar to 16%), catalase (CAT, similar to 84%) and glutathione (GSH, similar to 30%) contents. Habb-e-Asgand alone and in combination of paracetamol significantly (p<0.05, 0.01, 0.001) decreased LFT levels (20-25%), CYP activity (similar to 45%) and LPO level (similar to 25%), while it induced antioxidant enzyme activity (GR, similar to 15%; GPx, similar to 17%; GST, similar to 20% and CAT, similar to 60%). Discussion: Paracetamol metabolites may be mediating production of reactive oxidant species (ROS) and liver injury, which are attenuated by Habb-e-Asgand antioxidant constituents. Conclusion: Habb-e-Asgand may be used as a prophylaxis for ROS related liver injury.