Vascular dementia (VD) is the second most common type of dementia in the elderly. Currently, there are no effective drugs for preventing or decreasing the progression of dementia. Bilobalide (BB) is a monomer extracted from Ginkgo biloba leaves. The present study investigated the neuroprotective effects of BB in a two-vessel occlusion (2-VO)-induced VD rat model. The results showed that BB (4 and 8 mg/kg) significantly protected VD rats against cognitive deficits in the Morris water maze. Biochemical assessment showed that BB (4 and 8 mg/kg) increased superoxide dismutase (SOD) activity and glutathione (GSH) content, and decreased nitric oxide synthase (NOS) activity and malondialdehyde (MDA) content. Additionally, BB (4 and 8 mg/kg) was found to alleviate neuronal apoptosis and to reduce the expression of tumor necrosis factor-α (TNF-α) in the brain cortex and the hippocampal CA1 region in VD rats. These results suggest that BB provides protection against learning and memory impairment by reducing free radical injury and inhibiting neuronal apoptosis in the brain cortex and hippocampal CA1 region in VD rats.