Biologically inspired designs have become evident and proved to be innovative and efficacious throughout the history. This paper introduces a bio-inspired design of protective structures that is lightweight and provides outstanding crashworthiness indicators. In the proposed approach, the protective function of the vehicle structure is matched to the protective capabilities of natural structures such as the fruit peel (e.g., pomelo), abdominal armors (e.g., mantis shrimp), bones (e.g., ribcage and woodpecker skull), as well as other natural protective structures with analogous protective functions include skin and cartilage as well as hooves, antlers, and horns, which are tough, resilient, lightweight, and functionally adapted to withstand repetitive high-energy impact loads. This paper illustrates a methodology to integrate designs inspired by nature, Topology optimization, and conventional modeling tools. Two designs are explained to support this methodology: Helmet design inspired by human bone cellular structure (trabecular structure) and vehicle body inspired by a water droplet, ribcage, and human bone. In the helmet design, a finite part of is optimized using topology optimization to generate the porous structure. In the vehicle body design, a water droplet framework, the bio-inspired simulation-based design algorithm used in this work generates innovative layouts. At the vehicle scale, the generated spaceframe has a structure similar to the one of a long bone. In essence, the aerodynamic water droplet shape is protected by the specialized ribcage. At the component scale, each spaceframe tubular component is filled with a functionally graded cellular structure. This internal cellular structure reminds the one of a bone. The spaceframe is attainable with few parts of greater complexity. Such complex, lightweight, multiscale structural layout can be manufactured using 3D printing technologies.