The present study addresses the challenges of stiffness and strength design for large-opening structures in special configuration aircraft such as blended wing-body aircraft. By combining mechanical principles and numerical simulation methods, this research investigates the stability analysis of long-span opening load-bearing beams. A method for analyzing the buckling characteristics of opening beams under the influence of multiple elastic supports from frames is established, providing design requirements for frame stiffness. Additionally, the study explores the collaborative optimization of structural arrangement and stiffness for opening beams and frames. Through case studies, the interaction between frame spacing and cross-sectional parameters of beams and frames is revealed. Furthermore, the research conducts failure analysis and load-bearing capacity prediction for aircraft opening structures, developing a coupled failure analysis method using a Nastran-Abaqus based multi-level non-intrusive model coupling analysis. Experimental validation is performed using typical large-opening structure failure tests. Comparative results show that finite element simulation effectively captures the nonlinear load and deformation behavior during testing, with maximum errors of 8.8% and 7.1% in load and deformation predictions, respectively. The simulation results also demonstrate good agreement with experimental buckling phenomena and failure modes.