Stress induces a wide range of adverse effects on the central nervous system and is also associated with different neuropsychiatric disorders. The present study was aimed to explore the neuroprotective potential of methanolic extract of roots of Boerhaavia diffusa (MEBD) on various behavioral and biochemical parameters of stress. Sleep deprival stress and cold restrain stress were the models employed to induce stress. The experimental animals were subjected to both the stress conditions which led to impaired cognition, decreased motor and locomotor activity, induced depression in despair swim test. Both the stress models significantly increased oxidative stress in brain. Administration of MEBD significantly decreased the transfer latencies in elevated plus maze test. The duration of immobilization was also significantly decreased in animals treated with MEBD; indicating restoration of cognition and reduction of resultant depression. Boerhaavia diffusa reversed the effect of sleep deprival stress and cold restrain stress on the oxidative stress indices, indicating amelioration of stress. Boerhaavia diffusa attenuated behavioral and biochemical alterations associated with stress. Thus, Boerhaavia diffusa may be used for the treatment of neuropsychiatric disorders.