Background: Adults who have periodontitis are more likely to lose teeth, which affects their quality of life and causes masticatory dysfunction. Most people agree that smoking tobacco makes them more likely to get oral mucosal and periodontal diseases and makes the oral microbiome less balanced. Melatonin is a naturally occurring hormone that is released in a variety of organs. Objectives: To examine the relationship between smoking and salivary melatonin levels in periodontitis patients vs healthy people, and to establish a relationship between melatonin levels and periodontal parameters. Materials and methods: The study was conducted at the College of Dentistry, University of Baghdad, Baghdad, Iraq. The study period was from February to May 2022. There were a total of 74 male subjects aged 35-55 years, and they were divided into four different groups; Group 1: a control group of non-smokers (n = 12), Group 2: a control group of smokers (n = 12), Group 3: a group of individuals with periodontitis (n = 25), Group 4: a group of individuals with both periodontitis and a record of smoking (n = 25). A whole, unstimulated sample of the participant’s saliva (5 ml) was taken, and this was followed by an evaluation of clinical periodontal variables (probing pocket depth and clinical attachment level). To measure melatonin concentrations, saliva samples were biochemically analyzed using the Enzyme-Linked Immunosorbent Assay (ELISA). Results: Melatonin concentrations were shown to be lower in groups with periodontitis than in control groups, as well as lower in groups with smoking than in groups without smoking. It was found that there was a strong negative link between periodontal variables and the amount of melatonin in the saliva. Conclusion: According to this study, a reduced melatonin level was noticed in the salivary fluid of the smoker (healthy and periodontitis) groups in comparison with the non-smoker (healthy and periodontitis) groups. This suggests that active cigarette smoking had a retarding effect on the salivary levels of melatonin. [ABSTRACT FROM AUTHOR]