Vascular dementia (VD) is the second leading cause of cognitive impairment after Alzheimer's disease, posing a heavy burden to families and society. The majority of causes of VD are vascular diseases such as stroke, with ischemic stroke accounting for a large proportion. After ischemia-reperfusion, factors such as mitochondrial damage and increased xanthine oxidase lead to excessive production of reactive oxygen species (ROS) at the ischemic site, further exacerbating brain injury. Therefore, developing effective ROS scavengers is crucial. Polydopamine has become one of the widely used surface functionalized materials in recent years, due to its excellent biocompatibility and antioxidant properties. This paper proposed a macrophage membrane disguised polydopamine (PDA) nanoplatform for loading the neuroprotective drug puerarin (PUE). The as made PUE@PDA@CMs (PPCs) nanoplatforms can significantly and effectively clear ROS, alleviate oxidative microenvironment, and protect neurons from oxidative stress damage. The macrophage membranes modification enables PPCs to respond to lymphocyte recruitment at the site of cerebral ischemia-reperfusion injury, thereby targeting and aggregating to the injury site. In a mouse model of vascular dementia, PPCs treatment significantly reduced neuronal apoptosis and provided significant cognitive and memory function recovery, providing new strategies and prospects for the treatment of central nervous system diseases.