Cardiocerebral vascular disease (CCVD) is a common disease with high morbidity, disability, and mortality. Oxidative stress (OS) is closely related to the progression of CCVD. Abnormal redox regulation leads to OS and overproduction of reactive oxygen species (ROS), which can cause biomolecular and cellular damage. The Nrf2/antioxidant response element (ARE) signaling pathway is one of the most important defense systems against exogenous and endogenous OS injury, and Nrf2 is regarded as a vital pharmacological target. The complexity of the CCVD pathological process and the current difficulties in conducting clinical trials have hindered the development of therapeutic drugs. Furthermore, little is known about the role of the Nrf2/ARE signaling pathway in CCVD. Clarifying the role of the Nrf2/ARE signaling pathway in CCVD can provide new ideas for drug design. This review details the recent advancements in the regulation of the Nrf2/ARE system and its role and activators in common CCVD development. Copyright © 2020 Liangkai Cheng et al.