Prolonged separation of pups from their mother in early postnatal period can interfere with normal growth and development, resulting in different behavioral changes similar to features of schizophrenia in man. This study explored the cytoprotective action of kolaviron, a biflavonoid, on the prefrontal cortex and hippocampus of maternally deprived Wistar rats. Eight months old female rats were time-mated, and after delivery their pups were randomly assigned into four groups; group A received 0.5 ml of normal saline, group B received kolaviron orally (200 mg/kg/bw) on postnatal days (PND) 21–35, group C were maternally deprived on PND 9 for 24 hours, while group D were also maternally deprived on PND 9 for 24 hours, and then received kolaviron orally (200 mg/kg/bw) on PND 21–35. Behavioral studies (open field test, Morris water test, and Y-maze test) were conducted after the experiment prior to sacrifice. Some of the rats were anesthetized with ketamine and perfusion-fixed with 0.1 M phosphate buffered saline and 4% paraformaldehyde, while others were sacrificed by cervical dislocation for enzyme studies. The hippocampus and prefrontal cortex were excised from the brain and processed for tissue histology, histochemistry, and enzymatic analysis. Results revealed behavioral deficits, oxidative stress, degenerative changes, and astrocytosis in the prefrontal cortex and hippocampus of maternally deprived rats, but intervention with kolaviron caused significant improvement in neurobehavior, morphology, and neurochemistry in these brain areas. We concluded that kolaviron could protect the brain against neurological consequences of nutritional and environmental insults arising from maternal separation in early postnatal period.