Featured Application: Melatonin is a powerful antioxidant; it can bring numerous advantages to periodontal diseases, pursuing homeostasis, such as restoration of the concentration of antioxidants, reduction of periodontal inflammation with the regulation of inflammatory cytokines, reduction of oxidative stress, and significant reduction of bone resorption through the modulation of osteoclastic and osteoblastic activities. It was considered a reliable and feasible option as an adjunctive to the classical NSPT, obtaining a significative improvement of the periodontal parameters (PD, CAL, BOP, PI, and GI), a significative reduction of the pro-inflammatory proteins (IL-1b, IL-6, and TNF-α), and a better response for other biomarkers. Background: Melatonin is a hormone produced by the pineal gland, an endocrine gland located at the base of the brain. It acts as a powerful antioxidant; it can bring numerous advantages to periodontal diseases, pursuing homeostasis, such as restoration of the concentration of antioxidants, reduction of periodontal inflammation with the regulation of inflammatory cytokines, reduction of oxidative stress, and significant reduction of bone resorption through the modulation of osteoclastic and osteoblastic activities. Then, the goal of this integrative review was to evaluate the literature to better understand whether the use of melatonin is feasible to improve the non-surgical treatment of periodontitis. Methods: The integrative review was based on PICO strategy and PRISMA methodology. The focus question was: "Are there significant benefits in applying melatonin for the non-surgical treatment of periodontitis?" The PubMed, B-On, and Cochrane Library databases were enrolled, using the keywords melatonin, periodontal therapy, non-surgical treatment, and periodontitis, as associated with the Boolean connectors. The inclusion criteria were (i) CCT or RCT, (ii) adult population, (iii) full-text articles available, and (iv) in the last 10 years (2012–2022). The exclusion criteria were (i) animal studies, (ii) systematic review, and (iii) no other languages than English, Spanish, Portuguese, and Italian. A risk of bias was performed to assess the articles. Results: Initially, 2705 articles were identified. However, only six articles were included. From a total of 228 patients (109F and 119M) diagnosed with periodontitis, 22 patients dropped out (9.65%). The follow-up period varied between 8 weeks, 3 months, and 6 months. For clinical and molecular parameters, the melatonin group had significant and greater improvement (intragroup) and better data than the control group, which also had favorable results. There was low risk of bias for all studies. Conclusions: Within the limitation of this study, melatonin is a reliable and feasible option as an adjunctive to the classical NSPT, obtaining a significative improvement of the periodontal parameters (PD, CAL, BOP, PI, and GI), a significative reduction of the pro-inflammatory proteins (IL-1b, IL-6, and TNF-α), and a better response for other biomarkers. [ABSTRACT FROM AUTHOR]