The present study was designed to investigate the anti-genotoxic effect of Ocimum sanctum on fluoride induced genotoxicity and its impact on oxidative stress. Exposure to fluoride can mainly occur through drinking water when the levels far exceed the permissible limit. Fluorosis is a serious problem the world over resulting in damage to DNA. Micronuclei assessment from bone marrow and peripheral blood was used in the present study to assess the damage to DNA. Sodium fluoride in a single dose (30 mg/kg, i.p.) was used to induce micronuclei in albino mice. Treatment with the aqueous extract of Ocimum sanctum was initiated in the single dose study (100, 400 & 800 mg/kg) and as a time course for 1 day, 3 days and 7 days (100 mg/kg). 24 h after injecting sodium fluoride, the animals were sacrificed and micronuclei were determined from smears prepared from bone marrow and peripheral blood. The antioxidant impact of the extract was determined using ferric ion reducing capacity of plasma and thiobarbituric acid reactive substances as a measure of lipid peroxidation. All doses were capable of preventing the formation of micronuclei but 100 mg/kg of the aqueous extract was most efficacious as a single dose and in the time course study. The beneficial effect of Ocimum sanctum is possibly due to the synergistic action of constituents like polyphenols, triterpenoids, and flavonoids.