This paper takes metal bellows as the research object. Firstly, based on theory of forced vibration mechanics, the structural design parameters of metal bellows which have influence on vibration are accurately analyzed by the characteristics of mass matrix, stiffness matrix and damping matrix in the differential equation of vibration dynamics. Secondly, design range of the structural parameters is determined according to the system design boundary. The 18 groups of test schemes are designed by DOE and the vibration fatigue safety factor of the 18 groups of test schemes is calculated by the CAE vibration reliability analysis method. The regression analysis and response optimization method are used to calculate the optimal combination scheme of various structural parameters for the metal bellows with goal of maximizing the vibration fatigue safety factor. Finally, the optimal design scheme is verified by all the reliability tests. The optimal design method of metal bellows based on DOE ensures the metal bellows is designed correctly at one time, which shortens the R&D cycle, reduces the R&D cost and improves the efficiency of product design.