Hepatic injury elicits intracellular stress that leads to peroxidation of membrane lipids accompanied by alteration of structural and functional characteristics of membrane, which affect the activities of membrane-bound ATPases. The present study appraised the membrane protective effect of Premna tomentosa, a hepatoprotective drug used in Indian traditional medicine. Wistar strain rats were pre-treated with Premna tomentosa extract (750 mg/kg, orally) for 15 days, 24 h prior to administration of acetaminophen (640 mg/kg, orally). During acetaminophen intoxication, the levels of membrane-bound enzymes were significantly decreased, total ATPase (1.63-fold), Mg(2+)ATPase (1.9-fold), Ca(2+)ATPase (1.33-fold) and Na(+)K(+)ATPase (1.73-fold) which was accompanied by changes in the levels of inorganic cations N+, K+ and Ca2+. These alterations were prevented by Premna tomentosa extract pre-treatment, which shows that Premna tomentosa supplementation could exert a beneficial effect against liver injury-induced membrane damage. The potential of the plant might be credited to the presence of antioxidant compound limonene in the plant.