Background: Chronic cerebral hypoperfusion has been well characterized as a common pathological status contributing to vascular dementia (VD). In this study, the neuroprotective effect of modified Bo yang Hwan O Tang (mBHT), a polyherbal medicine for ischemic stroke, was investigated in a rat model for global ischemia. Materials and Methods: Global ischemia model was prepared in Sprague Dawley rats by the permanent occlusion of bilateral common carotid arteries (two vessel occlusion [2VO]) induced chronic cerebral hypoperfusion. mBHT at doses of 250 and 500 mg/kg was orally administrated for 4 weeks once a day, 24 h after 2VO. Histopathological change of the hippocampal region was observed by hematoxylin and eosin, Nissl, and Fluoro Jade B staining and immunohistochemistry with anti glial fibrillary acidic protein and anti neuronal nuclei antibodies. The expression of Bax, Bcl 2, and caspase 3 was investigated in the hippocampus by Western blot. The nuclear factor kappa B (NF κB) expression was also analyzed in hippocampal CA1 region using immunofluorescence staining. Results: The administration of mBHT at doses of 250 and 500 mg/kg significantly inhibited chronic cerebral hypoperfusion induced neuronal damage and astroglial activation in the hippocampal CA1 region in 2VO rats. mBHT increased the NF κB expression in the CA1 neuronal cells but decreased in activated astrocytes. In addition, mBHT significantly decreased the hippocampal expression of Bax and caspase 3 and increased the Bcl 2 expression in 2VO rats. Conclusions: Our data indicate that mBHT has a neuroprotective property in VD induced by chronic cerebral hypoperfusion through inhibiting the hippocampal neuronal damage and astrogliosis.