Phyllanthus amarus (P. amarus) is commonly used for traditional Indian medicine and as dietary adjuncts for the treatment of numerous physiological disorders including hepatic disorders. Due to the poor water solubility of its major constituents such as lignans and flavonoids, its absorption upon oral administration could be limited. The present study was designed to evaluate and compare the hepatoprotective effects of the ethanolic extract of P. amarus (PAE) and its nanoparticles (PAN) on paracetamol induced acute liver toxicity in Sprague-Dawley rats. An oral dose ofPAE at 125 and 250mg/kg and PAN at 25 and 50 mg/kg showed a significant hepatoprotective effect relatively to the same extent (P 0.001) by reducing levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and bile salts. These biochemical assessments were supported by rat hepatic biopsy examinations. Moreover, the results also indicated that the hepatoprotective effect of 50 mg/kg PAN was effectively better than 125 mg/kg PAE (P 0.00l), and an oral dose of PAN that is five times less than PAE could exhibit similar levels of outcomes. In conclusion, the authors suggest that the nanoparticles system can be applied to overcome other poorly water soluble herbal medicines and furthermore to decrease the treatment dosage.