Abstract: This study fabricates origami-inspired sandwich panels using 3D printing technology and investigates their blast resistance through explosion experiments. By examining different core layers, panel thicknesses, and equivalent loads, it is found that increasing the number of core layers enhances the specific energy absorption of the sandwich panel, while ribbed designs improve the stiffness of the core layer, thereby effectively enhancing the panel's resistance to deformation. Compared with uniformly distributed structures, gradient-designed cores significantly improve energy absorption capacity, offering an effective approach to enhance blast resistance. Overall, a gradient design with higher density in the upper layer of the origami core provides optimal protective performance under blast loading. This research offers a novel approach for applying origami structures in blast-resistant protective panels.