Background Stevia is a naturally occurring non-nutritive sweetener that has been reported as sugar substitutes for diabetic patients. We aimed to assess the impact of stevia supplementation on glycemic control in patients with type 2 diabetes mellitus (T2DM). Also, we aimed to examine the association between stevia supplementation and anthropometric measures as well as lipid profile in both obese and diabetic patients. Patients and methods The controlled clinical trial included unrelated 150 participants; 40 patients with T2DM and 60 obese patients and 50 healthy controls. Obese patients were then subdivided into two subgroups according to their fasting blood sugar: nondiabetic (n=30) and 30 patients with T2DM. The participants received stevia (4 mg/kg/body weight) as an alternative to artificial sweetener for 24 weeks. Results Our results found that stevioside supplementation for diabetic patients’ increased the total caloric intake and decreased BMI, waist circumference, waist–hip ratio, and fat mass index, in the obese group. Our results have shown a significant increase of BMI, waist circumference, waist–hip ratio, and fat mass index after 24 weeks of stevia supplementation. In the diabetic group, stevioside for 24 weeks improved the lipid profile and glycemic control, fasting plasma glucose, 2-h plasma glucose, fasting serum insulin, homeostasis model assessment of insulin resistance and hemoglobin A1c (HbA1c), as well as total cholesterol, triglycerides, low density lipoprotein-cholesterol, and high density lipoprotein-cholesterol in all studied intervention groups. Logistic regression test revealed that among clinical and laboratory waist circumference, fasting plasma glucose and HbA1c were independent predictors of response to stevioside. Conclusion Stevioside supplementations for 24 weeks improved cardiometabolic risk in diabetic patients. However, in the obese group, stevioside supplementations increased body weight.