In this study, we investigated the effects of phototherapy on the learning and memory abilities of sleep-deprived mice by establishing a sleep deprivation model. We discovered that sleep deprivation significantly decreased the learning and memory abilities of mice and produced anxiety-like behaviors, while the combination of 468 nm blue light treatment prevented the increase of inflammatory response, improved the antioxidant capacity of hippocampal tissue, regulated the expression of BDNF-TrkB signaling pathway genes, enhanced inter-synaptic transmission, and effectively improved the learning and memory abilities of mice.