Background: Carotenoids are a large group of natural pigments that occur in many foods, fruits, and vegetables. Several studies have shown a number of biological properties of carotenoids, particularly beneficial impacts on cancer, metabolic, neurodegenerative, and cardiovascular diseases. However, recent evidence has shown that these compounds could prevent, delay, and ameliorate diabetic retinopathy (DR). The aim of current study was to review the therapeutic effects of carotenoids in the treatment of DR and discuss the molecular mechanisms that are behind these pharmacological activities. Methods: Six online databases (Medline/PubMed, Scopus, Web of Knowledge, Embase, ScienceDirect, and ProQuest) were searched until September 2019. The systematic review was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Results: A total of 25 studies were included after the final retrieval. A relationship was observed between carotenoids and management of DR. Findings also demonstrated that the underlying mechanism of beneficial effects of these compounds was antioxidant, antiinflammatory, anti-angiogenic, and neuroprotective properties. Conclusion: Carotenoids potentially delay the initiation and prevent the progression of DR; however, ample preclinical studies are required to confirm their effect, and adequate clinical trials are needed to really understand how well these compounds influence DR among humans.