Introduction: Patients with chronic periodontitis exhibit significant interleukin-33 (IL-33) expression in their periodontal tissue. However, it is debatable, whether chronic periodontitis patients with gingival crevicular fluids (GCFs) have increased levels of IL-33. The ligand of the ST2 (suppression of tumorigenity) receptor is IL-33. The Toll-like receptor/IL-1R superfamily includes the ST2 receptor, which exists in two distinct versions; soluble ST2 (sST2), which is secreted, and ST2L, as a transmembrane form. In addition to measuring clinical parameters and correlating them with the levels of IL33 and sST2 in periodontitis patients, the goal of this study was to evaluate the levels of these two biomarkers in the GCF of patients with (stage I, II, and III) periodontitis relative to healthy controls. Objectives: The present study aimed to evaluate the levels of IL33 and sST2 in the GCF of individuals with periodontitis (stages I, II, and III) compared to those in healthy controls, and to assess clinical parameters and compare them to the sST2 and IL33 levels in patients with periodontitis. Materials and Methods: A total of 162 participants participated in the present study. Clinical measurements were made for the probing pocket depth (PPD), plaque index (PI), clinical attachment level (CAL), and bleeding on probing (BOP). The GCF was collected from each patient. To measure IL33 and sST2 levels, enzyme-linked immunosorbent assays (ELISAs) were used. Results: When comparing the periodontitis group to the healthy control group, the levels of IL33 and sST2 were greater (P>0.001). Only in the group with stage II periodontitis was there a significant association between PPD and sST2, whereas no significant correlation was detected between IL33 and periodontal markers. Conclusion: Compared to those of healthy controls, the GCF of periodontitis patients exhibited increased levels of IL33 and sST2. This finding implies that the pathogenesis of periodontitis and periodontal health are both influenced by IL33 and sST2.