Abstract: Origami sandwich structures exhibit excellent properties such as thermal insulation, noise reduction, vibration resistance, and weight reduction, demonstrating significant application potential in aircraft engines. However, complex loading environments and manufacturing processes can lead to debonding in the structure, significantly increasing its mechanical response under vibrational loads and posing a risk of fatigue failure. Therefore, studying the impact of debonding on the dynamic response of origami sandwich structures is of great importance. By integrating experimental tests and numerical simulations, this paper analyzes the dynamics of origami sandwich structures with debonding defects. The research results indicate: (1) As the debonding area expands, the natural frequency decreases, while the frequency response stress of the face sheet and core layer increases. When the debonding area reaches 40%, the fundamental frequency decreases by 1.3%, and the maximum frequency response stress of the face sheet and core layer increases by 2.49% and 106.05%, respectively. This is attributed to the reduction in overall structural stiffness and the redistribution of stress in the debonding region. (2) When the debonding area remains constant, moving the debonding location toward the fixed end reduces the fundamental frequency and increases the maximum frequency response stress of the core layer by 92.73%, significantly higher than that of the face sheet. This is primarily attributed to: the core layer's primary function as a shear transfer mechanism, debonding-induced alteration of load transmission paths triggering stress concentration, and the core's inherent susceptibility to deformation due to its thin-walled nature and complex geometric configuration. (3) Concentrated debonding and asymmetric debonding regions have a more pronounced impact on the dynamic response, specifically manifested in significant changes in stress distribution within the debonding region, with the maximum frequency response stress of the core layer increasing by approximately 120%.