The invention discloses a sleeper comprehensive optimization design method, and relates to the field of railway transportation. The method includes the following steps of A, conducting a comprehensivesimulating experiment, and selecting the optimal sleeper quality and railway structure parameters for making the overall rail structure dynamics response the lowest through a grey correlation method;B, obtaining detailed sizes of a sleeper with the parameter optimization region as the variable region according to the given sleeper design constraint conditions in the step A; C, returning the detailed sizes obtained in the step B to the step A, judging whether the current output quality is completely the same as the last output quality or not, and if not, executing the step B and the step C again until the completely the same quality and the matched rigidity value are output. The quality serves as the link of static load design optimization and dynamics optimization, the detailed sizes under the specific sleeper quality and the rail structure parameters for making the dynamics response the optimal under the specific sleeper quality are given finally, and the local requirements and theglobal optimum are combined.