There are multiple mechanisms of pathogenic factors in dementia and ischemic-reperfusion injury, such as oxidative stress (OS) and the reactive oxygen species (ROS). NADPH oxidases (NOXs) have a broad distribution in brain and participate in the oxidative stress and inflammatory responses. It may be efficient to treat this specific target of NOX to establish a balance between reactive oxygen species and antioxidants. This review will elaborate the possible relationship and mechanism between the occurrence of stroke and its complications and focus on NOXs, ROS and inflammatory responses to figure out the possible signaling pathway in the perspective of oxidative stress. And NOX2 will be focused to demonstrate the relationship between ischemia-reperfusion and pathogenic factors of dementia via the NOX2/ROS signaling pathway. And considering the upstream and downstream elements and the end results of this signaling pathway, inhibiting NOX2 activity can reduce oxidative damage and inflammatory responses, NOX2 can be considered as a drug target to treat stroke development to reduce the risk of severe dementia