The invention provides an alpha-mangostin derivative (I) and a preparation method thereof, and an application in preparation of neuroprotective drugs. The structural modification of alpha-mangostin iscarried out while a basic structure of alpha-mangostin is maintained to be unchanged in the alpha-mangostin derivative. Compared with alpha-mangostin, the modified new derivative has increased watersolubility and improved bioavailability. The alpha-mangostin derivative has good therapeutic effects on cerebrovascular diseases, and some derivatives are more active than a positive drug ibuprofen, so that the alpha-mangostin derivative has broad application prospects in the treatment of cerebrovascular diseases.