Aim: To estimate and correlate the salivary leucine-rich alpha-2 glycoprotein (LRG) in periodontitis patients with and without type 2 diabetes mellitus (T2DM). Materials and methods: A total of 75 subjects were selected and divided into three groups: the H group had 25 systemically and periodontally healthy subjects, the P group had 25 systemically healthy subjects with stage 3 grade C periodontitis, and the P + T2DM group had 25 patients with T2DM and stage 3 grade C periodontitis. Demographic variables and periodontal parameters were recorded, then unstimulated saliva samples were collected. The level of LRG was estimated using ELISA, and data were recorded and statistically analyzed. Results: On comparing the demographic variables and periodontal parameters between the groups, age, and BMI demonstrated a statistically significant difference between the three groups. The mean values of periodontal parameters and salivary LRG were significantly higher in the P + T2DM group [periodontal parameters: plaque index (PI)—2.48 ± 0.30, bleeding on probing (BOP)—72.20 ± 5.64, probing pocket depth (PPD)—7.26 ± 5.64, clinical attachment level (CAL)—7.71 ± 0.25, salivary LRG—385.6 ± 170.3] when compared to the P and H groups. The Spearman's correlation showed a strong positive correlation between salivary LRG levels and periodontal parameters. Conclusion: Within the limitations of this study, it can be inferred that salivary LRG has a role in proliferation, migration, and insulin resistance in diabetic and prediabetic patients. Thus, it can be used as a potential biomarker for early detection of T2DM in periodontitis patients. Clinical significance: Periodontitis and T2DM could influence the level of salivary LRG, and salivary LRG has a role in proliferation, migration, and insulin resistance in diabetic and prediabetic patients. Thus, it can be used as a potential biomarker for early detection of T2DM in periodontitis patients.