Effect of stress and its modulation by methanolic extract of bark of Alstonia scholaris was studied using acute restraint stress model in mice. The extract was also evaluated for nootropic and antioxidant potential to support anti-stress activity testing. Acute restraint stress resulted in significant increase of plasma corticosterone, glucose, protein, cholesterol and triglyceride levels in stress group of animals. Methanolic extract pretreatment at 100, 250 and 500 mg/kg for 7 days displayed promising anti-stress effect by normalizing these stress-induced biochemical perturbations in plasma of mice. Effect on cognitive functions was evaluated using passive avoidance model and elevated plus maze model. Pretreatment with extract at 100, 250 and 500 mg/kg augmented acquisition and retention of memory of learned task as evidenced by increased step-down and shortened-transfer latency in passive avoidance model and elevated plus maze model, respectively. Diazepam (2 mg/kg, ip) and piracetam (200 mg/kg, po) were used as standard drugs for anti-stress and nootropic activity testing. Further, the extract at 200 microg/ml showed maximum scavenging of stable radical 1,1-diphenyl, 2-picryl hydrazyl at 90.11% and nitric oxide radical at 62.77%. The present study, thus, provided scientific support for anti-stress (adaptogenic), antioxidant and nootropic activities of methanolic extract of bark of Alstonia scholaris.