Flavonoids have been extensively studied and reported to possess widespread biological activities, including antioxidant and chelating properties. They have been proposed to exert beneficial effects in a multitude of diseased states generated due to oxidative stress. Therapeutic efficacy of oral administration of Silymarin and Quercetin after fluoride exposure (50 ppm in drinking water for 45 days) was investigated in rats. Animals exposed to fluoride showed a marked enhancement in reactive oxygen species (ROS), a significant decrease in reduced glutathione (GSH) in blood. In brain and kidney also, a significant elevation in ROS and Thiobarbituric Acid Substances (TBARS) level was noted accompanied by a significant decline in reduced/oxidized glutathione (GSH: GSSG) ratio. Furthermore, significant protection was observed in altered neurotransmitters level following the administration of Silymarin and Quercetin. Interestingly, both the flavonoids were able to reduce the level of fluoride from blood and kidney suggesting that the two flavonoids have the ability to bind fluoride ion too. It can be concluded from the results that, post-treatment with these flavonoids not only significantly protects against fluoride-induced oxidative stress but reduce its burden too from blood and tissues.