Aim: Melatonin possesses antioncotic, anti-inflammatory, and immunomodulatory properties. It aids in the expression of matrix metalloproteinases (MMPs), reactive oxygen species (ROS), and growth factors and thereby inhibits invasion, endometriosis, and fibrosis. The objective of this study was to evaluate the effect of melatonin in topical gel formulation on the oral health and salivary nickel and chromium levels of patients undergoing fixed appliance therapy. Materials and methods: Sample consisted of 30 patients undergoing orthodontic fixed appliance therapy using metal brackets (12 ± 6.01 years). A novel melatonin-based oral gel was provided to the patients for use once daily for a period of 1 month. The salivary samples of patients were collected prior to and postgel usage and subjected to inductively coupled plasma optical emission spectrometry (ICP-OES), energy dispersive X-ray spectroscopy (EDS), and scanning electron microscopy (SEM). The independent t-test was used to compare the level of chromium and nickel in saliva, the plaque, and the gingival index pre and postadministration of the gel. Results: The results of the ICP-OES indicated that there was a reduction in both salivary nickel and chromium levels after the application of topical melatonin gel over a period of 1 month. The results, however, were not statistically significant (p > 0.005). A statistically significant result (p < 0.005) was observed with respect to the gingival index. Conclusion and clinical significance: The use of 2% topical melatonin gel in patients undergoing fixed appliance therapy showed a positive effect in terms of gingival and oral health and a reduction in salivary nickel and chromium levels.