Objective <p>To evaluate the effect of scaling and root planing (SRP) on clinical periodontal parameters and gingival crevicular fluid (GCF) levels of TNF-α, IL-1β, and IL-10 in periodontitis patients with and without diabetes.</p> Methods <p>A cross-sectional study was conducted involving 76 patients diagnosed with periodontitis, including 38 with diabetes and 38 without diabetes. All participants received standardized SRP treatment. Periodontal clinical parameters and glycated hemoglobin (HbA1c) levels (in diabetic patients) were recorded at baseline and three months post-treatment. GCF samples were collected to assess concentrations of TNF-α, IL-1β, and IL-10 using ELISA. Changes in inflammatory cytokine levels were compared between the two groups before and after treatment.</p> Results <p>SRP led to significant improvements in probing depth (PD), clinical attachment loss (CAL), bleeding index (BI), and plaque index (PLI) in both groups, with no significant intergroup differences. Diabetic patients showed a mean HbA1c reduction of 0.30 ± 1.24%. TNF-α levels significantly decreased in both groups post-treatment (<i>P</i> &lt; 0.001); however, post-treatment TNF-α levels remained significantly higher in the diabetes group than in the non-diabetes group (<i>P</i> &lt; 0.001). No significant changes were observed in IL-1β levels in either group. IL-10 levels increased more in the non-diabetic group than in the diabetic group, though the difference was not statistically significant (<i>P</i> = 0.422).</p> Conclusion <p>SRP treatment effectively improves periodontal clinical outcomes and modulates local inflammatory mediator levels. These findings highlight the need for individualized treatment strategies and interdisciplinary management in diabetic patients with periodontitis.</p>