Endplate design is important to the structural safety and the performance of the proton exchange membrane (PEM) fuel cells. In this paper, an organized design and analysis method is proposed to improve the endplate design. The 3D model for finite element analysis is constructed automatically by a CAD software with a parametric program through GUI interfaces. This model includes endplates, carbon plates, O-rings, gas diffusion layers (GDLs), and membrane electrode assemblies (MEAs). Then a series of finite element analysis are executed to analyze the structural behavior of PEM fuel cells. Structural boundary conditions and contact pairs are also applied into the meshed model. The positions of tie-bolts and parameters of endplate design are changed to improve the performance of PEM fuel cells through numerical optimization techniques. The structural behavior of key components is analyzed, including the compression ratio of GDLs, the sealing pressure of O-rings, and the structural safety of carbon plates. Results of analysis indicate that the shape of endplate affects the stack assembly pressure and contact behavior of PEM fuel cells. Proper shape of endplate can generate more uniform deformation of GDLs and avoid the leakage of fuels. With the changing design parameters of the endplate in the integrated design program, the optimum design that satisfies the design constraints and specifications can be found. According to the research conclusion, the proposed design and analysis method is helpful in determining the key dimensions for endplates or other components of PEM fuel cells.