Diabetes mellitus (DM) is a growing problem nowadays, and diabetic retinopathy (DR) is its predominant complication. Currently, DR diagnosis primarily relies on fundoscopic examination; however, novel biomarkers may facilitate that process and make it widely available. In this current review, we delve into the intricate roles of various factors and mechanisms in DR development, progression, prediction, and their association with therapeutic approaches linked to the underlying pathogenic pathways. Specifically, we focus on advanced glycation end products, vascular endothelial growth factor (VEGF), asymmetric dimethylarginine, endothelin-1, and the epigenetic regulation mediated by microRNAs (miRNAs) in the context of DR.