Silica‐fiber‐based sensors have the advantage of being small, electrically isolated, immune to electromagnetic fields, and easily incorporated into networks. However, only few of them were used for monitoring physiological signals directly, due to their limited sensitivity, comfort, and safety. In this work, a simple architecture for sensitive and wearable photonic sensors, which are capable of strain and pressure detection for healthcare applications is reported. The proposed sensor consists of a hybrid plasmonic microfiber knot resonator embedded in a polydimethylsiloxane membrane. The mechanical sensitivity is more than one order of magnitude larger than exhibited by traditional electronic devices or other fiber devices, including Bragg gratings. In addition, the sensing of wrist pulse, respiration, and finger pulse are also experimentally demonstrated. This novel photonic‐based platform may provide a new basis for designing sensitive and wearable sensors for personalized diagnostics and physiological monitoring applications. With their potential to be embedded into networks of smart clothing and remote health monitoring of patients, these sensors possessing great biocompatibility will have a distinguished advantage in military, aerospace, and medical applications, particularly in high‐magnetic‐field environments, e.g., magnetic resonance imaging.