The goal of the current study was to assess levels of salivary interleukin (IL)-38, IL-1β, and IL-10 in various periodontal clinical conditions. In total, 60 (20 healthy, 20 gingivitis, and 20 stage II–III, grade A–B periodontitis) subjects were included in the study. Demographic and clinical periodontal parameters were recorded. Samples were examined for IL-38, IL-1β, and IL-10 levels by means of enzyme-linked immunosorbent assay. Results demonstrated that the periodontitis group had significantly lower salivary IL-38 levels (P < 0.05) than the healthy group. Salivary IL-10 levels did not differ significantly between the groups (P > 0.05). The salivary IL-1β levels of gingivitis (P < 0.001) and periodontitis groups (P < 0.01) were significantly higher than those of the healthy group. The present study indicated that IL-38 level is decreased in periodontal disease. The results suggested a possible role of IL-38 in the periodontal inflammation process. Clarifying the mechanisms of IL-38 in the inflammatory process may contribute to the development of novel treatment strategies in periodontal diseases.