High sensitivity and biocompatibility have always been the performance pursued of Intelligent sensor of human health signals. One of the best ways in this regard is non-invasive, which requires wearable and ultra-sensitive biosensors. Mesoscopic reconstruction endows Silk fibroin (SF) with excellent mechanical properties, biocompatibility and thermostability by incorporating Polyurethane (PU) into the meso-structures of SF via intermolecular templated nucleation. The gelation process of SF is observed in situ to prove the inducing effect of PU in the self-assembly process of SF. The SF/PU co-crystal films are given conductivity by physical vapor deposition to obtain sensors and smart wristbands. The flexible pressure sensor shows a high sensitivity of 0.48 kPa−1 under the pressure from 0 Pa to 1500 Pa. The smart wristband can detect the body information reflected in the human wrist, such as the wrist meridian response caused by finger movement, and the pulse signals at the wrist.