Background: Paracetamol overdose causes severe hepatotoxicity via oxidative stress. Natural antioxidants from edible insects like termites remain underexplored. Odontotermes obesus is traditionally consumed but lacks scientific validation for liver protection.

Objective: To evaluate the hepatoprotective activity of Odontotermes obesus ethanolic extract against paracetamol-induced liver damage in Wistar rats.

Methods: Termites were collected, identified, and extracted with 70% ethanol. Phytochemical screening was performed. Acute oral toxicity was tested per OECD 423. Thirty male Wistar rats were divided into five groups (n=6): normal control, paracetamol control (2 g/kg), silymarin (100 mg/kg) + paracetamol, extract low dose (250 mg/kg) + paracetamol, extract high dose (500 mg/kg) + paracetamol. Treatments were given orally for 7 days; paracetamol on day 7. Serum ALT, AST, ALP, total bilirubin, total protein, and liver homogenate GSH, SOD, CAT, MDA were measured. Liver histopathology was scored.

Results: Paracetamol significantly (p<0.05) elevated ALT (342.5 vs 42.3 U/L), AST (298.7 vs 85.6 U/L), ALP (245.6 vs 98.2 U/L), bilirubin (2.45 vs 0.52 mg/dL), and MDA (9.8 vs 2.1 nmol/g), while reducing total protein (3.8 vs 7.1 g/dL), GSH (2.1 vs 6.8 μmol/g), SOD (6.2 vs 18.4 U/mg), and CAT (8.3 vs 22.1 U/mg). Odontotermes obesus extract at 500 mg/kg significantly reversed all parameters (ALT 89.6 U/L, GSH 5.6 μmol/g, MDA 3.5 nmol/g), comparable to silymarin. Histopathology showed reduced necrosis and inflammation.