The invention discloses a preparation method of sugammadex. The method comprises the steps of carrying out substitution by adopting fully halogenated gamma-cyclodextrin and 3-(chlorosulfonyl) propionate under the action of alkali to generate 2-ester ethyl sulfuryl-gamma-cyclodextrin; reducing under the action of a reducing agent metal and anhydrous alcohol to generate 2-ester ethyl sulfydryl-gamma-cyclodextrin; and finally adding sodium hydroxide to generate the sugammadex. The preparation method of the sugammadex is simple in operation, the reaction conditions are easy to control, the yield is relatively high and the preparation method has a wide application prospect.