To investigate the crashworthiness and energy absorption characteristics of aircraft fuselage substructures and to conduct structural crashworthiness design, this study focuses on a typical metal aircraft fuselage as the research object. A drop test of a typical fuselage substructure was performed, and the energy absorption characteristics were evaluated based on both experimental and simulation analysis results. Subsequently, an energy absorption design for the fuselage substructure was developed. The influence of structural layout parameters on the crash response of the new fuselage substructure was examined through simulation analysis. Comparisons were made regarding structural deformation, impact force-time curves, acceleration responses, and energy absorption for fuselage substructures with different layout parameters. The results indicate that during the crash process of the original structure, the primary energy absorption modes include plastic deformation and fracture in the column, frame, and beam connection areas, bending deformation of cabin floor beams, and failure of connectors. Since all columns bend and break near the connection areas, the other parts of the columns are almost entirely free of plastic deformation, resulting in limited energy absorption by the columns. The new substructure proposed in this study features a novel configuration that fully leverages the advantages of metal plastic deformation. Compared to the original configuration, the new substructure exhibits more uniform deformation while maintaining the same total mass of the fuselage structure. It significantly reduces the peak load and acceleration at the early stage of the crash. The proportion of energy absorption by the frame and energy-absorbing components has increased markedly. After optimization, the average overload of the new fuselage substructure is reduced by 30.8% compared to the original configuration. The average acceleration of the two mass points on the cabin floor of the new fuselage substructure is reduced by 25.0% and 37.6%, respectively, compared to the original configuration. These findings provide valuable insights and references for the crashworthiness design of aircraft fuselage substructures.