Fluorosis is an endemic health problem for both humans and livestock in some parts of the world including India. This fast expanding problem needs remedial measures. Though limited reports suggest ameliorative effect of boron (B) and calcium (Ca) against fluoride (F) toxicity in animals, still there is a need for long duration study to understand the possible mechanism of action. Here, we did the same; studied the ameliorative effect of B and Ca on F toxicity in Wistar strain (Rattus norvegicus) rats. Forty-eight male Wistar albino rats were divided randomly into six groups. The group T1 was given normal water (control) while the groups T2-T6 were supplemented with F through water @ 30 ppm (as sodium fluoride), 30 ppm F+ 50 ppm B (as sodium borate), 50 ppm B, 30 ppm F+ 50 ppm calcium chloride and 50 ppm calcium chloride, respectively. After four months, all the rats were sacrificed and blood, teeth, femur bone and liver were collected and analyzed for mineral content. Fluoride toxicity significantly (P <0.05) reduced phosphorus content in bone, calcium content in liver, and superoxide dismutase (SOD) activity in plasma. However, F toxicity significantly (P <0.05) increased phosphorus and glucose content in plasma, and calcium and magnesium content in teeth and fluoride content in liver. Boron and calcium chloride as ameliorating agents significantly (P <0.05) reduced the fluoride content in all the internal organs and also significantly reduced the elevated level of glucose and phosphorus in plasma and improved SOD activity in plasma. It is concluded that toxic effect of F is partially ameliorated by supplementation of 50 ppm of B or CaCl2.