Aim: To evaluate the serum level of endothelin-1 (ET-1) and lipid profile in chronic periodontitis patients before and after periodontal therapy. Materials and Methods: Sixty systemically healthy patients were divided into two groups, each with 30 patients. Group A with 30 healthy individuals and Group B with 30 chronic periodontitis patients. Group B was further divided into Group B1 and Group B2. Group B1 consisted of 15 patients with clinical attachment loss (CAL) of 1–2 mm treated by nonsurgical periodontal therapy. Group B2 of 15 patients with CAL of 3–4 mm, treated by periodontal flap surgery. Blood samples were collected before and 3 months following periodontal treatment to determine the serum level of ET-1 and lipid profile. Results: There was a statistically significant difference in ET-1 and lipid profile levels before and after periodontal treatment in both Groups B1 and B2. However, the difference was more significant in Group B2 than Group B1 (P < 0.001). Conclusion: Serum ET-1 and lipid profile could be a potential biomarker for periodontal and cardiovascular diseases. Periodontal therapy could reduce the risk of cardiovascular disease by reducing ET-1 and lipid profile postoperatively. © 2025 Elsevier B.V., All rights reserved.