Abstract Background The objective of this study was to compare the levels of gingival crevicular fluid (GCF), salivary, and serum matrix metalloproteinase‐9, interleukin (IL)‐17, IL‐36γ, and IL‐38 in individuals with healthy periodontium, gingivitis, and periodontitis and to evaluate their correlations with clinical periodontal parameters. Materials and Methods Ninety systemically healthy and nonsmoking volunteers divided into a healthy (H) group ( n = 30), a gingivitis (G) group ( n = 30), and a periodontitis (P) group ( n = 30) were included in this study. Clinical periodontal parameters of volunteers were recorded, and GCF, unstimulated saliva, and serum samples were collected. Data analysis was done with enzyme‐linked immunosorbent assays. The Kruskal–Wallis test and Bonferroni correction were used for multiple comparisons and post hoc statistical analyses. Results The group H had significantly lower clinical parameters than the group P ( p < 0.001). GCF and salivary IL‐36γ and IL‐38 levels were significantly higher in the group P than in the H and G groups ( p < 0.05). Positive correlations between biochemical findings and clinical periodontal parameters were observed. Conclusions IL‐36γ and IL‐38 levels in GCF, saliva, and serum correlate with clinical periodontal parameters and may play a role in determining the activity of periodontitis.