Stiffened panels are common load-bearing structures in aircraft fuselage and wings. Under axial compression and fuselage bending loads, they are susceptible to buckling failure, which limits the structural safety and aircraft service life. Empirical formula is often used for engineering calculations in aircraft structural static strength assessment. The engineering calculation of load-carrying capacity for stiffened panels is closely related to the selection of end support coefficients for fuselage frame structures. In the development of existing aircraft models, typically conservative end support coefficients are chosen, resulting in excessive structural safety margins and weight redundancies, hindering further advancements in aircraft lightweight design. To address the problem, this study first establishes a simulation calculation model for end support coefficients of typical aircraft panel structures based on slitting method, using Euler’s buckling theory. Subsequently, the coupled relationship between end support coefficients and the interaction between stiffened panel structures and supporting frame segments is analyzed in depth. Furthermore, the influence structural characteristic parameters such as frames and longitudinal stiffeners on end support coefficients is analyzed, and integrated buckling-resisting optimization designs of aircraft panel structure are conducted for frames, longitudinal stiffeners-skin, and frame-skin-longitudinal stiffener configurations. Finally, the effectiveness of buckling-resisting optimization designs for typical panel structure is validated through additive manufacturing of scaled-down specimens and axial compression tests. The established simulation and optimization methods in this study effectively enhance the buckling resistance of aircraft panel structures, offering significant opportunities for improving aircraft performances.