Recently, traditional polymer-based surgical meshes have drawn unwanted attention as a result of host tissue complications arising from infection, biocompatibility, and mechanical compatibility. Seeking an alternative solution, we present a hierarchically structured nanofibrous surgical mesh derived from the naturally woven cocoon of the Japanese giant silkworm, termed MothMesh. We report that it displays nontoxicity, biocompatibility, suitable mechanical properties, and porosity while showing no adverse effect in animal trials and even appears to enhance cell proliferation. Hence, we assert that the use of this natural material may provide an effective and improved alternative to existing synthetic meshes.