Age-related macular degeneration (AMD) is one of an increasing number of diseases that causes irreversible impairment and loss of vision in the elderly. AMD occurs by oxidative stress-mediated apoptosis of retinal pigment epithelium cells. The onset of AMD may be positively correlated with the exposure to blue light. We screened food-derived carotenoids for cytoprotective action against blue light irradiation using human ARPE-19 retinal pigment epithelium cells. This study revealed that blue light irradiation triggered apoptosis and oxidative stress in all--retinal (atRAL)-exposed ARPE-19 cells by generating singlet oxygen (O), leading to significant cell death. We found that astaxanthin, a potent anti-oxidative xanthophyll abundant in several marine organisms including microalgae, salmon, and shrimp, significantly suppresses blue light-induced apoptotic cell death of atRAL-exposed ARPE-19 cells by scavenging O. Mechanistic studies using the blue-light irradiated cells also demonstrated that the cytoprotective effects of astaxanthin can be attributed to scavenging of O directly. Our results suggest the potential value of astaxanthin as a dietary strategy to prevent blue light-induced retinal degeneration including AMD.