Diabetes, a worldwide health concern while burdening significant populace of countries with time due to a hefty increase in both incidence and prevalence rates. Hyperglycemia has been buttressed both in clinical and experimental studies to modulate widespread molecular actions that effect macro and microvascular dysfunctions. Endothelial dysfunction, activation, inflammation, and endothelial barrier leakage are key factors contributing to vascular complications in diabetes, plus the development of diabetes-induced cardiovascular diseases. The recent increase in molecular, transcriptional, and clinical studies has brought a new scope to the understanding of molecular mechanisms and the therapeutic targets for endothelial dysfunction in diabetes. In this review, an attempt made to discuss up to date critical and emerging molecular signaling pathways involved in the pathophysiology of endothelial dysfunction and viable pharmacological management targets. Importantly, we exploit some Traditional Chinese Medicines (TCM)/TCM isolated bioactive compounds modulating effects on endothelial dysfunction in diabetes. Finally, clinical studies data on biomarkers and biochemical parameters involved in the assessment of the efficacy of treatment in vascular endothelial dysfunction in diabetes was compared between clinically used western hypoglycemic drugs and TCM formulas.