A typical flow field plate of a large-scale proton exchange membrane fuel cell (PEMFC) can be divided into a reaction zone, a distribution zone (DZ), and a collection zone (CZ). This paper presents the comprehensive design optimization of the DZ and CZ (DCZ) through topology optimization (TO) and other numerical methods, elucidating the pivotal role of a reasonably-designed DCZ in ensuring the optimal performance of a large-scale PEMFC. A two-dimensional surrogate model was introduced for the TO process, which involved a combination of continuous free flow and electrochemically active porous flow, with the depth-averaging method. Subsequently, a three-objective TO was employed for novel symmetric DCZ design through density mapping. The three-dimensional two-phase model confirmed that the optimized DCZ structure had a beneficial impact on the power, pressure drop, and flow uniformity of the PEMFC. In conjunction with the volume of the fluid model, the drainage efficiency of the cell was found to be markedly enhanced by 22.8 %. The present study will be helpful for the future design of commercial large-scale PEMFCs to achieve better performance.