Implantable medical electronic devices (IMEDs) have attracted great attention and shown versatility for solving clinical problems ranging from real‐time monitoring of physiological/ pathological states to electrical stimulation therapy and from monitoring brain cell activity to deep brain stimulation. The ongoing challenge is to select appropriate materials in target device configuration for biomedical applications. Currently, silk‐based biomaterials have been developed for the design of diagnostic and therapeutic electronic devices due to their excellent properties and abundant active sites in the structure. Herein, the aim is to summarize the structural characteristics, physicochemical properties, and bioactivities of natural silk biomaterials as well as their derived materials, with a particular focus on the silk‐based implantable biomedical electronic devices, such as implantable devices for invasive brain‐computer interfaces, neural recording, and in vivo electrostimulation. In addition, future opportunities and challenges are also envisioned, hoping to spark the interests of researchers in interdisciplinary fields such as biomaterials, clinical medicine, and electronics.