MicroRNA-126 (miR-126) has emerged as one of the most extensively studied microRNAs in the context of human diseases, particularly in vascular disorders and cancer. Its high degree of conservation across vertebrates underscores its evolutionary significance and essential functional roles. Extensive research has been devoted to elucidating the molecular mechanisms through which miR-126 modulates key physiological and pathological processes, including angiogenesis, immune response, inflammation, tumor growth, and metastasis. Furthermore, miR-126 plays a causal role in the pathogenesis of various diseases, serving as potential biomarkers for disease prediction, diagnosis, prognosis and drug response, as well as a promising therapeutic target. In this review, we synthesize findings from 283 articles, focusing on the roles of miR-126 in critical biological processes such as cell development, survival, cycle regulation, proliferation, migration, invasion, communication, and metabolism. Additionally, miR-126 represents a promising candidate for miRNA-based therapeutic strategies. A comprehensive understanding and evaluation of miR-126 are crucial for advancing its clinical applications and therapeutic potential.