Chronic stress if not manage properly results to major depression disorder which has profound impact on individual's life quality and deeply related to suicide death worldwide. This serious mental disorder is closely linked to the hippocampus due to it functionality in the regulation of cortisol production. Abelmoschus Esculentus (A. Esculentus) possess polyphenols, terpenoid and polysaccharides, indication the presence of anti-stress and antioxidant activities. This study examine if A. Esculentus can ameliorate stress-induced damages on the structure and hippocampus associated function, using fluoxetine treatment as a baseline. Forty-eight young male Wistar rats (80 ± 10 g) were divided into 6 groups (n= 8). Group-A received feed and water only, Group-B received 300 mg/kg of A. Esculentus and Group-C received 10 mg/kg of fluoxetine, for 14 days respectively, while Group-D were stressed for a period of 21 days, Group-E were stressed for 21 days followed with 300 mg/kg of A. Esculentus for 14 days and F were stressed for 21 days followed with 10 mg/kg of Fluoxetine for 14 days after. Chronic stress exposure (group-D) significantly depleted final body weight and increased the brain weight. It reduced lines crossed and middle squares crossed performance, while it increased the number of unaided rearing and immobility time performance significantly. GPx1 was significantly down-regulated and GSR obviously reduced. Further, it is noteworthy that chronic stress exposure caused histopathological changes in the hippocampus CA-1 area, presenting neurons with disorganized arrangement, apoptotic-like appearance, as well as shrunken and condensed cytoplasm. Glial fibrillary acidic protein (GFAP) staining demonstrated astrogliosis and KI-67 expression revealed high reduction in the degree of cell proliferation. Thus, treatment with A. Esculentus improved hippocampal integrity by inhibiting the underlying mechanisms of stress induced damages in this study. Conclusively, our findings put A. Esculentus as a potential target for tackling stress-induced depression.