Based on the working principle of depolarizer, the general relationship between the structural parameters of depolarizer and the polarization sensitivity of optical system is established by applying Mueller matrix and Stokes vector. With numerical analysis, it is pointed out that the depolarizer has excellent depolarization performance when the angle between the optical axes of two wedge crystals is 90°. Under this orientation, selecting proper crystal thickness can further reduce the polarization sensitivity of optical system. Finally, taking grating imaging spectrometer as an example, we design a depolarizer and evaluate its performance.