Biological material systems have developed unique combinations of mechanical properties to fulfill their specific functions through a series of ingenious designs. Specifically, natural organisms have evolved a diversity of weapons during the long-term evolutionary “arms race” in generating an exceptional mechanical efficiency with a synergy of effective offense and persistence—two characteristics that often tend to be mutually exclusive in many synthetic systems. Taking lessons from nature may offer new promise for creating novel materials with unprecedented properties. This review elucidates the categories, forms, structures and mechanical properties of nature’s weapons, and extracts the design principles for achievement of both offensive and defensive properties from the perspective of materials science. We also revisit the new advances in replicating these design principles at different length-scales in artificial materials, devices and tools, and discuss the challenges and opportunities associated with the study on biomechanics and bioinspired materials.