Abstract: Alstonia scholaris (Apocynaceae) is an important constituent of numerous ayurvedic preparations. The present study was aimed to evaluate the modulatory effects of Alstonia scholaris on biochemical and antioxidant parameters in acetaminophen (APAP) induced hepatotoxicity. Hepatic biomarkers viz. aspartate and alanine aminotransferases (AST, ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), Gamma Glutamyl Transferase (GGT), paraoxonase (PON1), arylesterase (AE), ceruloplasmin (CP), bilirubin, plasma proteins and oxidative stress biomarkers like Total Oxidant Status (TOS), Total Antioxidant Status (TAS), blood glutathione (GSH), total thiols (TTH), glucose-6-phosphate dehydrogenase (G6PDH), malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and Glutathione-S-Transferase (GST) activities were estimated to assess the extent of hepatic damage induced by APAP and the protection imparted against it by leaf extracts. Oral administration of APAP, hepatotoxicity indicated by increased (p<0.05) activities of AST, ALT, ALP, GGT, G6PDH, total bilirubin and TOS while decreased TAS, CAT, SOD, GPx, GST, TTH, GSH, PON1, AE, TTH, direct bilirubin, total plasma proteins and albumin in plasma was observed. The treatments with either aqueous or ethanolic leaf extract of A. scholaris restored the activities of ALT, GGT, ALP, LDH, PON1, AE, G6PDH, GPx, CAT, GSH, TTH, TAS and MDA in APAP induced hepatotoxicity. Hepatic and oxidative damage biomarkers indicated that treatments with aqueous or ethanolic leaf extract minimized APAP induced hepatic damage. High correlation coefficients between PON1/AE ratio and TTH levels and increased TAS, GSH levels suggests ethanolic extract to have higher hepatoprotective potential compared to aqueous extract of A. scholaris.