Objectives <p>The present study aimed to examine the effects of dietary intake of total, animal-based, and vegetable-based protein on cardiometabolic risk factors in diabetic patients, using iso-energetic substitution models.</p> Methods <p>This cross-sectional study was a part of the Ravansar Non-Communicable Disease (RaNCD) cohort study with 8,894 subjects. Univariate and multivariate logistic regression models were used to determine the associations between total, animal, and vegetable protein intake (per 5% energy) and cardiometabolic risk factors. All analyses were carried out at a 95% confidence level using STATA software version 14.2.</p> Results <p>In diabetic patients, higher intake of total protein increased the risk of hypertension by 2.48 times compared to the reference group (<i>p</i> = 0.03). Besides, the association between the consumption of one unit of energy (5% energy) from protein at the expense of one unit of energy from fat and the risk of cardio-metabolic risk factors, showed an increase in dyslipidemia and CVDs by 65 and 48%, respectively. The substitution for carbohydrates also causes a reduction in obesity and abdominal obesity by 28 and 53%, respectively.</p> Conclusion <p>In diabetic and non-diabetic patients, different associations were observed following the substitution of protein. In diabetic patients, the substitution protein for fat increased the risk of dyslipidemia and CVDs and carbohydrate replacement increased the risk of dyslipidemia. The highest vs. the lowest intake of animal protein decreased the risk of obesity and abdominal obesity, whereas regarding plant protein a direct link was found with dyslipidemia. However, prospective studies are needed to clarify the cause-and-effect links.</p>