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Adropin is a peptide involved in the regulation of glycolipid metabolism, contributing to improved glucose homeostasis and the mitigation of dyslipidemia. The objective of this study is to ascertain whether there is a discrepancy in the expression of microRNA-21 (miRNA-21) and adropin levels in Type 2 diabetes mellitus (T2DM) patients who also exhibit macro- and micro-vascular complications (nephropathy, neuropathy, retinopathy) were also observed to uncomplicated diabetes patients and healthy individuals; to explore the relationship between serum adropin and miR-21, endothelial dysfunction, and carotid intima-media thickness (CIMT). The present study comprised 89 patients with T2DM (microvascular n = 24, macrovascular n = 20, uncomplicated type 2 n = 45) and 19 non-diabetic coronary artery disease (CAD). The control group was composed of 20 healthy individuals. Expression of miRNA-21 in all diabetic patients was significantly higher than control group, while adropin levels were found to be significantly lower. No significant difference was observed between the diabetic patient groups with microvascular complications and those without complications regarding miRNA-21 and adropin levels. The miR-21 expression and adropin levels of the non-complicated diabetic group and only the coronary disease group were significantly higher and lower than the control group. CIMT was significantly higher in patients with macrovascular complications and non-diabetic CAD than in the other groups. A positive correlation was found between miR-21 and CIMT, whereas a moderate negative correlation was detected between miR-21 and adropin levels. The present study indicated that adropin and miR-21 can be equally good markers both in separating diabetic patients with macrovascular complications from the healthy group. In the meantime, the endothelial cell is an important target, and endothelial dysfunction is important in diabetic vasculature. Increased miR-21 expression and decreased adropin levels can be explained by the damage that hyperglycemia causes to the endothelium in diabetic patients.