For the cracks generated during the three-point bending process of a large aluminum alloy non-equal thickness panel, the reason for the cracks was analyzed by software ABAQUS simulation, which was the changes in thickness of panel thick zone and transition zone, as well as the stress concentration on the heading crossbeam. Then, two structural optimization schemes were proposed, and the stress and strain distribution characteristics in each scheme during the bending process of non-equal thickness panels were analyzed by combining the numerical simulation with experiment. The results show that the gradual change in width of circumferential ribs improves the compression resistance of circumferential ribs near the thick zones and reduces the stress concentration. The moderate extension of the thick zone can solve the problem of difficult plastic forming due to excessive stiffness in the thick zone. The combination of both results in the most uniform distribution of three-point bending normal stress and shear stress and reduce the shear stress. At the same time, the problem of warping caused by the excessive thickness changes in the original model and the simple gradual change scheme of circumferential rib is solved.