Fluoride (F-) is becoming an ineluctable environmental pollutant causing deleterious effects in humans. In the present study, we examined whether tamarind seed coat extract (TSCE) is beneficial against the F--induced systemic toxicity and hematological changes. Wistar rats were randomly grouped as follows: group I served as control; group II intoxicated with sodium fluoride (NaF, 300ppm) in drinking water; group III was administered through oral intubation with TSCE (100mg/kg bw); group IV was treated with NaF (300ppm) in association with TSCE (100mg/kg bw) for 30days. The results indicated that F- exposure induced oxidative stress as evidenced by elevated levels of reactive oxygen species and lipid peroxidation in the brain, liver, and kidney. F- administration modulates hematological indicesWBC, RBC, and mean corpuscular volume. Moreover, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, acetylcholinesterase, and monoamine oxidase significantly increased on F- exposure. Conversely, -aminolevulinic acid dehydratase and glutathione/reduced glutathione ratio were decreased. Activity of antioxidantssuperoxide dismutase, catalase, glutathione peroxidase, and vitamin Cwas also significantly decreased due to F- administration. Treatment with TSCE effectively mitigated the alterations through its antioxidant potential. The data suggested that the TSCE had beneficial effects in alleviating the F--induced toxicity and hence can serve as a promising neutraceutical agent.