Various neuroprotective drugs, including diverse natural extracts and synthetically producted compunds, can improve the physiological state of neuronal cells in the penumbra during ischemic stroke (IS), thereby reducing permanent brain damage. However, it is challenging for these neuroprotective drugs to efficiently accumulate in the penumbra upon administration. Various drug carriers derived from natural biological membranes can be engineered through multiple approaches, enabling not only customizable loading of drugs but also high targeting precision, thereby exerting neuroprotective effects. This article reviews research progress on the engineering methods and purposes of modifying natural membrane carriers, and outlines future directions for in-depth investigation of this therapeutic approach.