The glass sponge is a porous lightweight structure in the deep sea. It has high toughness, high strength, and high stability. In this work, a super-depth-of-field microscope was employed to observe the microstructure of the glass sponge. Based on its morphological characteristics, two novel bio-inspired lightweight structures were proposed, and the finite-element analyses (FEA) of the structures were carried out under compression, torsion, and bending loads, respectively. The structure samples were fabricated using stereolithography 3D-printing technology, and the dimension sizes of the samples were equal to those of the corresponding FEA models. Mechanical tests were performed on an electronic universal testing machine, and the results were used to demonstrate the reliability of the FEA. Additionally, lightweight numbers (LWN) were proposed to evaluate the lightweight efficiency, and a honeycomb structure was selected as the reference structure. The results indicate that the lightweight numbers of the novel bio-inspired structures are higher than those of the honeycomb structure, respectively. Finally, the proposed structures were optimized by the response surface, BP (Back Propagation) and GA-BP (Genetic Algorithm optimized Back Propagation) method. The results show that the GA-BP model after training has a high accuracy. These results can provide significant guidance for the design of tube-shaped, thin-walled structures in the engineering.