Menopause is a natural aging process characterized by decreased levels of sex hormones in females. Deprivation of estrogen following menopause results in alterations of dendritic arborization of the neuron that leads to neurobehavioral complications. Hormone replacement therapy is in practice to manage postmenopausal conditions but is associated with a lot of adverse effects. In the present study, the efficacy of buckwheat tartary (Fagopyrum tataricum) whole seed extract was investigated against the neurobehavioral complication in middle-aged ovariectomized rats, which mimic the clinical postmenopausal condition. Hydroalcoholic extraction (80% ethanol) was done, and quantification of major marker compounds in the extract was performed using HPLC. Oral treatment of the extract following the critical window period rescued the reconsolidation process of spatial and recognition memory, as well as depression-like behavior. Gene expression analysis disclosed elevated oxidative stress and neuroinflammation that largely disturb the integrity of the blood-brain barrier in ovariectomized rats. Gfap and Pparγ expression also showed reactive astrogliosis in the rats subjected to ovariectomy. The extract treatment reverted the elevated oxidative stress, neuroinflammation and expression of the studied genes. Furthermore, protein expression analysis revealed that Gsk-3β was activated differentially in the brain, as suggested by β-catenin protein expression, which was normalized following the treatment with extract and rescued the altered neurobehavioral process. The results of the current study concluded that Fagopyrum tataricum seed extract is better option to overcome the neurobehavioral complications associated with the menopause.