A case–control study was conducted, including 88 participants equally allocated into four groups ( n  = 22 each): healthy nonsmokers, healthy smokers, nonsmokers with periodontitis, and smokers with periodontitis. Unstimulated whole saliva samples were collected, and periodontal status was assessed using plaque index (PI), bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment loss (CAL). Subsequently, samples were analyzed for HIF‐1a, E‐CAD, and N‐CAD levels using enzyme‐linked immunosorbent assay (ELISA). Statistical analyses included intergroup comparisons, Spearman’s correlation analysis, diagnostic performance evaluation using receiver operating characteristic (ROC) curve analysis, and mixed‐effects model analysis.

Salivary E‐CAD and N‐CAD levels were significantly higher in the periodontitis groups than in the healthy groups ( p   < 0.05), whereas HIF‐1α showed no significant differences among the study groups ( p   > 0.05). All clinical periodontal parameters were significantly elevated in participants with periodontitis. ROC analysis demonstrated acceptable discriminatory performance for E‐CAD and N‐CAD, whereas HIF‐1α showed variable performance. N‐CAD yielded the highest discrimination between periodontal health and periodontitis (area under the curve [AUC] = 84.5%), while E‐CAD showed the highest discrimination between healthy smokers and nonsmoking participants with periodontitis (AUC = 85.9%). Although salivary E‐CAD levels were descriptively lower in smokers with periodontitis than in nonsmokers with periodontitis, this difference was not statistically significant.

Salivary E‐CAD and N‐CAD were significantly altered in periodontitis and demonstrated greater potential than HIF‐1α for reflecting periodontal disease status. The absence of significant differences in salivary HIF‐1α levels among the study groups may indicate limited ability to reflect localized periodontal hypoxic changes. HIF‐1α also showed limited and inconsistent associations with EMT‐related biomarkers, with a significant positive correlation observed only between HIF‐1α and N‐CAD in the periodontitis group. Smoking was associated with alterations in biomarker profiles, particularly E‐CAD levels. Overall, salivary EMT–related biomarkers may serve as promising noninvasive indicators of periodontal disease, although further validation is required.