Chronic hyperglycemia and vascular damage are strictly related. Biomarkers of vascular damage have been intensively studied in the recent years in the quest of reliable cardiovascular risk assessment tools able to facilitate risk stratification and early detection of vascular impairment. The present study is a narrative review with the aim of revising the available evidence on current and novel markers of hyperglycemia-induced vascular damage. After a discussion of classic tools used to investigate endothelial dysfunction, we provide an in-depth description of novel circulating biomarkers (chemokines, extracellular vesicles, and epigenetic and metabolomic biomarkers). Appropriate use of a single as well as a cluster of the discussed biomarkers might enable in a near future (a) the prompt identification of targeted and customized treatment strategies and (b) the follow-up of cardiovascular treatment efficacy over time in clinical research and/or in clinical practice.