The aim of this study was to investigate the effects of Ginkgo biloba extract (EGb 761) on oxidative stress and the histopathological changes in brain tissues of mice exposed to fluoride administration. A total of 24 mice were divided into 4 groups as control, EGb 761, fluoride and fluoride+EGb 761, with 6 mice in each group. Control group received drinking water, fluoride group received 50 mg/L fluoride in drinking water, fluoride+EGb 761 group was given 50 mg/L fluoride in drinking water and 20 mg/kg EGb 761 orally by gavage, and EGb 761 group was given only 20 mg/kg EGb 761 orally by gavage for 30 days. At the end of the experimental period, the levels of malondialdehyde (MBA) and glutathione (GSH) as well as' the activities of superoxide dismutase (SOD) and catalase (CAT) were detected, and histopathological examination was conducted in the brain of mice. The results showed that the levels of MDA, GSH, and the activities of SOD and CAT in fluoride group were statistically higher than in the control group. However, no statistically significant difference was detected between fluoride+EGb 761 and control group. The neurodejenerative changes seen in fluoride group were not detected in fluoride+EGb 761 group. It was concluded that the toxic effect of fluoride was related to the formation of reactive oxygen species, and EGb 761 had a protective effect by preserving antioxidant enzymes activity in mice brain tissues. Ginkgo biloba extract also prevented the histopathological changes induced by fluoride administration.