The characterization of silkworm and spider silk from nanometer to micrometer scale by atomic force microscopy reveals similar design principles despite the distance of their spinning organisms in evolutionary terms. Nanoglobules are the basic microstructural blocks in both materials, but this common microstructural design is tuned to fulfill the biological function of each silk. Spider silk nanoglobules are isotropic, and its size varies during stretching. Silkworm silk nanoglobules are anisotropic and loosely aligned with the fiber axis. The combination of our results with previous data on the structure of silks at a molecular level allows a model of the supramolecular organization of both silkworm and spider silk to be proposed. The detailed characterization of the microstructure of natural silks should contribute to the development and production of a new family of bioinspired fibers.