Carbon fiber reinforced plastic (CFRP) composites have gained particular interests due to their high specific modulus, high strength, resistance to environment, lightweight. In the automotive industry, numerous studies have been ongoing to replace the metal component with CFRP for the purpose of weight saving. One of the significant benefits of CFRP laminates is the ability of tailoring fiber orientation and ply thickness to meet the acceptable level of structural performance with little waste of material capability. This study focused on the concurrent optimization of ply orientation and thickness for CFRP laminated engine hood, which was based on the gradient-based discrete material and thickness optimization (DMTO) method. Two manufactural constraints, namely contiguity and intermediate void constraints, were taken into account in the optimization problem to reduce the potential risk of cracking matrix of CFRP. The design objective was the minimization of the mass of the CFRP hood subject to stiffness and eigenfrequency constraints under multiple load cases. To predict the pedestrian safety performance of the CFRP hood, the simulation of pedestrian head impact on the CFRP hood was carried out in terms of national standard of China. A prototype of the CFRP hood was fabricated by vacuum assisted resin transfer molding (VARTM), and the experimental tests were then conducted to validate the numerical results of the optimum design. The results demonstrated that the framework of the concurrent optimization of the CFRP hood and the numerical analysis of pedestrian safety offers a pragmatic procedure for the achievement of lightweight design with CFRP materials.