Diabetic retinopathy (DR) is a multifactorial neuro-microvascular disease, whose prevalence ranges from 25% to 60% of subjects affected by diabetes mellitus, representing the main cause of legal blindness in adults of industrialized countries. The treatment of advanced stage of DR is based on invasive and expensive therapies, while few strategies are available for the early stage or prevention. The mechanisms underlying DR involve a complex interplay between the detrimental effects of hyperglycemia, dyslipidemia, hypoxia, and oxidative stress, providing several pathways potentially targeted by nutrients and nutraceuticals. In this study, we conducted a systematic review of observational and interventional studies, evaluating the effect of nutrients and/or nutraceuticals on the risk of DR and their potential use for the treatment of patients with DR. The analysis of the 41 included studies (27 observational and 14 interventional studies) suggests a promising preventive role of some nutrients, in particular for vitamins B (i.e., B1 and B12), D, and E. However, further investigations are necessary to clarify the potential clinical application of nutraceuticals in the prevention and treatment of DR.