New biomarkers are currently promising to improve cardiovascular risk (CVR) prediction to prevent cardiovascular complications and their associated morbidity and mortality. In practice, homocysteine (Hcy) and vitamin D (Vit D) have shown statistical associations with the incidence of cardiovascular events. Our study aimed to investigate the association between each of these biomarkers and atherosclerosis and to evaluate their contribution to the stratification of CVR in type 2 diabetic patients (T2D). Methods: This was a cross-sectional and comparative study that included 53 T2D patients with at least one cardiovascular disease (CVD) and 67 T2D patients without any CVD. Measurements of Hcy and 25-OH Vit D were obtained for 116 and 71 patients, respectively. Hyperhomocysteinemia (HHC) was defined as a level greater than 15 μmol/L, and Vit D deficiency was defined as a level below 10 ng/mL. Results: The average level of Hcy was 27.65 ± 31.95 μmol/L. It was significantly correlated with age (p = 0.008), body mass index (p = 0.008), fasting blood glucose (p Conclusion: Our study demonstrated an association between Hcy, macroangiopathy, and coronary artery disease in T2D patients; however, Vit D was not effective in diagnosing these conditions.