both strongly associated with vascular and metabolic complications. Endothelin-1 is a potent vasoconstrictor that plays a key role in vascular tone regulation and endothelial function. Objective: To evaluate serum Endothelin-1 levels, lipid profile parameters (total cholesterol, LDL-C, VLDL-C, HDL-C, triglycerides), and HbA1c in patients with type 2 diabetes and essential hypertension compared with healthy controls, in order to assess their association with vascular injury and metabolic risk. Methods: A case-control study was conducted in the Department of Biochemistry, College of Medicine, University of Baghdad. Between November 2024 and February 2025, a sample of patients were recruited from Baghdad Teaching Hospital and Ibn Al-Bitar Center for Cardiac Surgery Hospital. A study on 180 adult males (aged 40–50 years), divided into three groups: 60 with type 2 diabetes mellitus (Group A), 60 with essential hypertension (Group B), and 60 healthy controls (Group C). Blood samples were collected after an overnight fast for measurement of HbA1c, lipid profile, and Endothelin-1 using a Sandwich-ELISA kit. Results: Significant differences were observed among the three groups. Group A showed markedly higher HbA1c, triglycerides, and VLDL-C, along with significantly lower HDL-C compared with Groups B and C. Both Groups A and B had significantly elevated total cholesterol and LDL-C compared with controls. Endothelin-1 levels were significantly higher in diabetics than in hypertensive patients and controls. Conclusion: Both diabetes and hypertension impair metabolic health, with diabetes showing more severe effects on lipid metabolism and glycemic control. Elevated endothelin-1 levels in diabetics may contribute to increased vascular risk, highlighting the need for early metabolic monitoring and intervention.