The invention provides a 3-droperidol derivative represented by a structural formula (I), wherein R is hydrogen, C1-C6 alkyl, aryl, benzyl, or a structure as the formula; R1 is hydrogen, C1-C18 alkyl, aryl, benzyl or hydroxymethyl; R2 is C1-C6 alkyl, aryl, benzyl or alkoxy; substitution positions of R2 on a benzene ring are 2-, 3-, 4-, 5-, 6- sites or a plurality of sites; and the previous groups are not substituted or substituted by one or more substituents selected from alkyl, alkyl halide, hydroxyalkyl, halogen, alkoxy, or hydroxyl. The invention also provides a preparation method of the 3-droperidol derivative. The preparation method is novel, the raw materials and the reagents are cheap, the reaction conditions are mild, and the operations are easy. With the method, produced 1-substituent-3-droperidol can be used as an important intermediate in novel medicine developing.