In this article, a novel re-entrant octagonal honeycomb (ROH) with negative Poisson's ratio (NPR) configuration is proposed owing to its superior energy absorption and lightweight design performances. Regarding the effects of adjacent unit cells, a mechanics-based homogenization approach is put forward and employed to derive static mechanical properties including elastic modulus and Poisson's ratio of two-dimensional (2D) and three-dimensional (3D) ROHs under axial loading. Based on above, the predominant compression failure mode is explored. Then, the static mechanical properties and finite element model of ROH are validated by experiment and demonstrate high accuracy. Subsequently, to obtain dynamic responses of the ROH under dynamic impact loading, the relations among dynamic plateau stress and quasi-static plateau stress, initial density, dense strain and impact velocities are established under the conditions of mass conservation and momentum theorem based on one-dimensional shock wave theory and ideal rigid-perfectly plastic material model. Besides, dynamic energy absorption models of the ROH under dynamic loading are acquired in consideration of the effects of impact velocities on dense strain, the results show that theoretical models agree quite well with simulation results. On this basis, the application of ROH on automotive energy absorber is studied with the purpose of acquiring superior energy absorption and satisfying lightweight requirements simultaneously. Based on the decoupling thought of stiffness and pedestrian protection, a new design method of carbon fiber reinforced plastics (CFRP) hood with ROH is put forward in consideration of energy absorption and lightweight requirements. Of this, ROH is regarded as sandwich structure to meet the demands of energy absorption, CFRP plates are treated as outer and inner skins to satisfy the needs of stiffness. Firstly, multi-objective optimization models are set up under the constraints of reasonable structural parameters and negative Poisson’s ratio. Then, the NSGA-Ⅱalgorithm is adopted to achieve the optimal Pareto fronts with the targets for maximum unit mass energy absorption and minimum density. Afterwards, the optimization on thicknesses of CFRP layers is carried out to achieve minimum mass under the constraint conditions that the static stiffness of CFRP hood is larger than that of steel hood. In addition, the layering sequence of inner and lower skins are also optimized. Finally, improved overall stiffness, optimized HIC values and similar lightweight space of CFRP hood with ROH are achieved in comparisons with CFRP hood without ROH. Compared with steel hood, the pedestrian protection performance of CFRP hood with ROH is greatly enhanced, 1st free mode increases by 33.9%, and torsional stiffness and bending stiffness increase by 23.1% and 30.8%, respectively. While the weight decreases by 40.1%. The results indicate that the CFRP hood with ROH presents outstanding advantages of pedestrian protection and lightweight design in terms of HIC and stiffness performance.