Dry eye, the most common ocular surface disease, can cause ocular surface tissue damage and discomfort symptoms and seriously affect people’s quality of life. The etiology of dry eye is diverse, and its pathogenesis is complex. The oxidative stress reaction is considered to be among the important factors in the pathogenesis of dry eye. Therefore, activating the antioxidant system has a potential therapeutic effect on dry eye. Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway is considered the most important antioxidant pathway in the body. The activation of the Nrf2 signaling pathway and its interaction with other pathways are important mechanisms to prevent the occurrence and development of dry eye. This review describes the structure and function of Nrf2, summarizes the changes in the oxidative stress response in dry eye, focuses on the potential mechanism of the Nrf2 signaling pathway in the treatment of dry eye, and, finally, summarizes the drugs that activate the Nrf2 signaling pathway in the treatment of dry eye.