BackgroundIt has been stated that microRNA (miRNA) plays an important role in development, homeostasis, and immune functions, and abnormal miRNA expression may cause faster disease progression. ObjectiveThe aim of this study was to determine miR-203, miR-142-3p, miR-146a, miR-146b, miR-155, and miR-29b gene expressions in the saliva of smokers and non-smokers with the periodontal disease before and after non-surgical periodontal therapy (NSPT). MethodsA total of 90 individuals, 30 with periodontitis, 30 with gingivitis, and 30 periodontally healthy (control group), were included. These three groups were divided into subgroups as smoking and non-smoking individuals, with 15 people in each group. NSPT was applied to patients with periodontitis and gingivitis. Saliva samples and clinical parameters were obtained at baseline and repeated 6 weeks after NSPT. ResultsSaliva miR-203, miR-142-3p, miR-146a, miR-146b, and miR-155 gene expressions were significantly upregulated in patients with periodontal disease compared to the control group both in smokers and non-smokers, and also these miRNAs' gene expressions were significantly higher in the periodontitis group than in the gingivitis group at baseline (p < .05). A significant increase in saliva miR-142-3p expression was detected in all groups of smokers compared to non-smokers (p < .05). Although there was a decrease in salivary miRNAs gene expressions with the treatment, it was not statistically significant (p > .05). ConclusionsThese results suggest that salivary miR-146a, miR-146b, miR142-3p, miR-155, and miR-203 gene expressions increased with the progression of periodontal disease, but unchanged after periodontal treatment. Moreover, smoking may contribute to an increase in the levels of salivary miR-142-3p in the periodontal health and disease.