The sandwich panel structures have been widely used in many industrial applications because of their high mechanical properties. The middle layer of these structures is very important factor in controlling and enhancing their mechanical performance under various loading scenarios. The re-entrant lattice configurations, are prominent candidates that can be used as the middle layer in such sandwich structures because of several reasons namely the simplicity in tuning their elastic (e.g., values of Poisson’s ratio and elastic stiffness) and plastic (e.g., high strength-to-weight ratio) properties by only adjusting the geometrical features of the constituting unit cells. Here, we investigated the response of a three-layered sandwich plate with a re-entrant core lattice under flexural bending using analytical (i.e., zig-zag theory), computational (i.e., finite element) and experimental tests. We also analyzed the effects of different geometrical parameters (e.g., angle, thicknesses, and length to the height ratio of unit cells) of re-entrant lattice structures on the overall mechanical behavior of sandwich structures. We found that the core structures with auxetic behavior (i.e., negative Poisson’s ratio) resulted in a higher bending strength and a minimum out-of-plane shear stress as compared to those with conventional lattices. Our results can pave way in designing advanced engineered sandwich structures with architected core lattices for aerospace and biomedical applications.