Wearable devices rely on hybrid mechanisms that possess the advantages of establishing a smarter system for healthcare, sports monitoring, and smart home applications. Socks with sensing capabilities can reveal more direct sensory information on the body for longer duration in daily life. However, the limitation of suitable materials for smart textile makes the development of multifunctional socks a major challenge. In this paper, we have developed a self-powered and self-functional sock (S-sock) to realize diversified functions including energy harvesting and sensing various physiological signals, i.e., gait, contact force, sweat level, etc., by hybrid integrating poly(3,4-ethylenedioxythiophene) polystyrenesulfonate (PEDOT:PSS)-coated fabric triboelectric nanogenerator (TENG) and lead zirconate titanate (PZT) piezoelectric chips. An output power of 1.71 mW is collected from a PEDOT:PSS-coated sock with mild jumping at 2 Hz and load resistance of 59.7 MΩ. The study shows that cotton socks worn daily can potentially be a power source for enabling self-sustained socks comprising wireless transmission modules and integrated circuits in the future. We also investigate the influences of environmental humidity, temperature, and weight variations and verify that our S-sock can successfully achieve walking pattern recognition and motion tracking for smart home applications. On the basis of the sensor fusion concept, the outputs from TENG and PZT sensors under exercise activities are effectively merged together for quick detection of the sweat level. By leveraging the hybrid S-sock, we can achieve more functionality in the applications of foot-based energy harvesting and monitoring the diversified physiological signals for healthcare, smart homes, etc.