Objective <p>Periodontitis and type 2 diabetes mellitus (T2DM) are chronic diseases with a well-established bidirectional relationship. Recent studies have focused on salivary biomarkers to better understand their shared inflammatory mechanisms. This study aimed to assess salivary levels of asprosin, interleukin (IL) -39, IL-40, and IL-1β in patients with and without periodontitis and/or diabetes.</p> Materials and methods <p>Eighty-eight participants were classified into four groups based on periodontal and diabetic status. Unstimulated saliva samples were collected and analyzed by ELISA. In addition to clinical periodontal parameters, body mass index (BMI) and glycated hemoglobin (HbA1c) levels were recorded.</p> Results <p>Salivary asprosin and IL-1β levels were elevated in periodontitis groups regardless of T2DM status and showed positive correlations with BMI. IL-39 showed no significant findings. All biomarkers, with the exception of IL-39, were positively correlated with clinical periodontal parameters. IL-40 was elevated in both diabetic and non-diabetic patients with periodontitis.</p> Conclusions <p>Elevated salivary asprosin, IL-40, and IL-1β levels in diabetic individuals with periodontitis may indicate their involvement in the inflammatory interactions linking metabolic dysfunction and periodontal tissue breakdown. IL-39 showed limited utility. These findings enhance understanding of salivary inflammatory patterns in diabetes-associated periodontitis, although the saliva-only, cross-sectional design warrants cautious interpretation.</p> Clinical relevance <p>The identification of salivary asprosin, IL-40, and IL-1β as potential indicators of periodontal and metabolic inflammation suggests that saliva-based testing could support non-invasive screening and monitoring in patients with diabetes and periodontitis.</p> Clinical trial number <p>NCT06735313.</p>