This study was conducted to determine whether feeding a diet containing excess crude protein (CP) or calcium (Ca) for up to 120 days can ameliorate the effects of fluoride (F) intake on bone health and thyroid function observed in rabbits fed a CP- and Ca-deficient diet. Treatment with F increased serum bone Gla protein concentrations and effects of F were reversed within 60 days in animals fed a high Ca diet. Feeding either a high CP or high Ca diet for 60–90 days increased combined cortical thickness (CCT) and the ratio of CCT to medullary canal diameter (MCD) in the midshaft of the femur of F treated animals. Bone mineral content was also reduced in response to F treatment and effects of F were reversed in animals fed a high CP diet for 30 days. Feeding a high Ca diet reversed F-induced alterations in serum TSH concentrations on day 30 and day 120 and on serum T3 levels by day 90. In contrast, F-induced elevations in serum T4 at day 30 and day 60 were reversed in animals fed a high CP or high Ca diet. Although no effect of F treatment on serum free T3 levels was noted, free T4 was elevated on day 30 in response to F treatment and the F-induced elevation in free T4 was not observed in animals fed a high CP diet. These results demonstrate divergent protective effects of high CP and high Ca diets on adverse indices of bone metabolism and thyroid function induced by F treatment in rabbits fed a CP- or Ca-deficient diet.