INTRODUCTION: The worldwide prevalence of type 2 diabetes mellitus (T2DM) and obesity has been steadily increasing over the past four decades, with projections indicating a significant rise in the number of affected individuals by 2045. Therapeutic interventions in T2DM aim to control blood glucose levels and reduce the risk of complications. Dietary and lifestyle modifications play a crucial role in the management of T2DM and obesity. While conventional medical nutritional therapy (MNT) often promotes a high-carbohydrate, low-fat Mediterranean diet as an elective treatment, low-carbohydrate diets (LCDs), specifically those restricting carbohydrate intake to less than 130 g/day, have gained popularity due to their multifaceted benefits. Scientific research supports the efficacy of LCDs in improving glycemic control, weight loss, blood pressure, lipid profiles, and overall quality of life. However, sustaining these benefits over the long term remains challenging. This trial aimed to compare the effects of a Mediterranean diet vs. a low-carbohydrate diet (carbohydrate intake < 130 g/day) on overweight/obese patients with T2DM over a 16-week period. The study will evaluate the differential effects of these diets on glycemic regulation, weight reduction, lipid profile, and cardiovascular risk factors. METHODS: The study population comprises 100 overweight/obese patients with poorly controlled T2DM. Anthropometric measurements, bioimpedance analysis, and blood chemistry assessments will be conducted at baseline and after the 16-week intervention period. Both dietary interventions were hypocaloric, with a focus on maintaining a 500 kcal/day energy deficit. RESULTS: After 16 weeks, both diets had positive effects on various parameters, including weight loss, blood pressure, glucose control, lipid profile, and renal function. However, the low-carbohydrate diet appears to result in a greater reduction in BMI, blood pressure, waist circumference, glucose levels, lipid profiles, cardiovascular risk, renal markers, and overall metabolic parameters compared to the Mediterranean diet at the 16-week follow up. CONCLUSIONS: These findings suggest that a low-carbohydrate diet may be more effective than a Mediterranean diet in promoting weight loss and improving various metabolic and cardiovascular risk factors in overweight/obese patients with T2DM. However, it is important to note that further research is needed to understand the clinical implications and long-term sustainability of these findings.