Aim: Several recent studies have indicated that a number of salivary biomarkers seem to be compromised in smokers with periodontal disease. The aim of this study is to assess salivary levels of cyanide and thiocyanate in Syrian patients with chronic (ChP) and aggressive (AgP) periodontitis, and to investigate the effect of smoking on these two biomarkers. Material and methods: The study population comprised 162 individuals allocated within four groups: chronic periodontitis (ChP), elderly control group (EC), aggressive periodontitis (AgP), Young control group (YC). All participants were asked to follow certain rules for at least 2 hours before the collection of morning samples of unstimulated whole saliva. Levels of Cyanide (CN) and thiocyanate (SCN) were estimated using a spectrophotometer. Statistical analysis was performed to examine differences between study groups. Results: Salivary CN and SCN levels were significantly higher in AgP and ChP groups compared to healthy subjects. Smokers in disease groups had a significant increase in CN and SCN compared to nonsmokers. Conclusion: This study exhibited significantly elevated levels of salivary CN and SCN in smokers with periodontitis as opposed to nonsmokers. Clinical significance: Salivary CN and SCN could be considered as important indicators for monitoring periodontitis.