Background Estrogen deficiency in postmenopausal period causes severe neuroendocrine changes in brain which influences memory and other nervous functions. Anthocleista schweinfurthii is used traditionally to treat female infertility and menopause related symptoms. This study was performed to investigate the potential neuroprotective effects of aqueous extract of Anthocleista schweinfurthii on brain in a postmenopause-like model of ovariectomized Wistar rats. Methods Thirty animals were sham-operated or ovariectomized (Ovx) 84 days after surgery, six groups of five rats each were daily treated orally during 28 days with: distilled water for groups 1 (sham-operated) and 2 (Ovx), estradiol valerate (group 3) and the three doses of extracts {groups 4, 5 and 6 (Ovx)}. Biochemical and histological evaluations focused on brain. Results Compared to sham-operated control, ovariectomy decreased total protein levels in brain (p<0.01) which was increased by plant extract at the dose of 300 mg/kg (p<0.05), underlying its anabolic properties. Ovariectomy significantly decreased magnesium levels in brain (p<0.001). Anthocleista schweinfurthii increased significantly magnesium levels (p<0.01), showing its capacity to act on synaptic conduction. Ovariectomy induced oxidative stress by increasing malondialdehyde levels (p<0.05) and decreasing reduced glutathione levels (p<0.05) in brain. The plant extract exhibited antioxidative activity by reducing malondialdehyde levels and increasing glutathione levels in brain. Damage in brain structure which was caused by ovariectomy disappeared following the treatment. Conclusions Results suggest that Anthocleista schweinfurthii may have neuroprotective effects in Ovx Wistar rats by increasing total protein, magnesium levels and reducing oxidative stress in brain.