Introduction Periodontitis is a chronic inflammatory infection in which tissue destruction is associated with an imbalance between oxidant-antioxidant systems. Melatonin is an antioxidant biomarker that has an antioxidant action. Nonsurgical treatment is one periodontal treatment method that affects etiologic factors. This study investigated salivary melatonin concentration and its changes following nonsurgical treatment in periodontal disease. Materials and methods This study is a case control one where the study groups included 45 patients with periodontal disease and 15 healthy subjects selected as controls. Unstimulated saliva was collected before and after scaling and root planing. Sample was evaluated by radioimmunoassay (RIA) method. In order to analyze the data t-test, ANOVA was used. The p < 0.05 was considered significant. Results Melatonin was detected in study group before nonsurgical treatment. Salivary melatonin levels in the severe periodontitis group were significantly lower than the other groups (p < 0.05). The melatonin changes were statistically significant between the groups of patients after intervention. The significant correlation between salivary melatonin with the clinical parameter was observed (p < 0.05). Conclusion Nonsurgical treatments improve clinical parameters. Salivary melatonin level has correlation with changes in clinical parameters. The melatonin production after nonsurgical treatment had correlation with severity of disease. How to cite this article Hagh LG, Yousefimanesh H, Mohammadi F, Ahangarpour A. Evaluation of Nonsurgical Treatment Effects on Salivary Melatonin Level in Periodontal Disease: A Radioimmunoassay Study. World J Dent 2013;4(4):217-223.