Aim: To avoid enamel demineralization, orthodontists generally prescribe fluoridated agents to their patients. The effects of fluorides on underlying biological tissues are not well-known. Previously published literature on animal studies provides evidence of fluorides modifying calcium metabolism. This study analyzes the effects of fluoridated mouthwashes and toothpastes on calcium metabolism in orthodontic patients. Materials and methods: A prospective randomized trial allocated 90 subjects to two treated groups (30 each), one group using non-fluoridated toothpaste and the other group using fluoridated toothpaste and mouthwashes and a control group with no intervention. All patients had uniform bracket prescriptions and were treated with similar archwire sequences. Blood samples at four specific time periods (before treatment,1 week, 30 days, and 6 months) were collected in a heparinized syringe and centrifuged to retrieve serum plasma. Serum thus collected was assessed for any alterations in calcium levels using a calcium test kit and comparisons of changes were made. Results: Maximum decrease in serum calcium levels were noted at 7 days in both fluoridated and non-fluoridated groups, although the results were not statistically significant at p < 0.001. Conclusion: The use of fluoride agents during fixed orthodontic therapy does not carry significant risk in alteration of calcium metabolism. However, known hypocalcemic patients can be given additional calcium supplements to avoid hypocalcemia. Additionally, this mild decrease in serum calcium could also favor the rate of orthodontic tooth movement. However, further studies are required in order to provide evidence for the same. Clinical significance: Fluoride containing oral hygiene agents should be used with caution in patients with decreased calcium levels.