In this study, novel sandwich core designs with bio-inspired reinforcements were proposed and their bending behaviors were comparatively examined. The geometrical shapes of alligator osteoderm and chambered nautilus shell were utilized as bio-inspired reinforcements for sandwich core structures. Sandwich core structures were produced through the additive manufacturing method. Experimental tests and finite element analysis were performed to determine the bending performances of the proposed sandwich core structures. The load-carrying capacity, deformation ability, damage-tolerant capability, energy absorption, and damage mechanisms of the proposed sandwich core structures were comparatively investigated through experimental and numerical methods. The orthotropic material model and Hashin’s damage criterion were used in the numerical model of 3D-printed sandwich core structures to consider the effect of the filament raster orientation on the elastic and damage behavior of the sandwich core structures. Compared to the classical honeycomb sandwich core structure, while bio-inspired reinforcements improved the load-carrying capacity and damage-tolerant capability of sandwich core structures, they reduced the energy absorption ability of sandwich core structures due to reducing the vertical deformation ability of sandwich core structures. Bio-inspired reinforcements significantly affected the stress distribution and damage behavior of the sandwich core structures. They reduced von Mises stress level at the outer cell edges of the sandwich core structures and caused reinforcement damage instead of outer cell damage.