<p>Diabetes is a metabolic disorder primarily characterized by hyperglycemia, posing a substantial global health concern. Insulin resistance significantly contributes to the pathogenesis of type 2 diabetes and its associated complications, such as cardiovascular diseases and dyslipidemia. MicroRNAs (miRNAs), critical regulators of gene expression, have emerged as essential mediators in diabetes and its related pathological conditions. Among these, miR-126 is particularly important for vascular homeostasis and endothelial function. Dysregulated expression of miR-126 is closely associated with impaired angiogenesis, endothelial dysfunction, and the accelerated progression of diabetic complications. This review comprehensively examines the diverse roles of miR-126 in diabetes and its microvascular complications, emphasizing the mechanisms by which miR-126 modulates pivotal signaling pathways implicated in the pathophysiology of diabetes. By integrating miRNA-mRNA interactions with protein-protein interaction networks in diabetic microvascular complications, this study highlights the central role of miR-126 in gene regulation and associated pathophysiological events. The “AGE-RAGE signaling pathway in diabetic complications” emerged as the most significantly enriched pathway, with AKT1, BCL2, MAPK1, TP53, and SIRT1 identified as critical common target genes involved in these processes. Collectively, these insights underscore the therapeutic potential of miR-126 in managing and treating diabetes and associated complications.</p>