Abstract Collagen fiber skeleton from animal skin is an ideal substrate for electronic skin (e‐skin). However, the interface mismatch between conductive materials and skeleton and the monotonicity of conductive network still hinder its creation. Herein, a novel collagen fiber‐based e‐skin with dual‐mode conduction of NaCl and conductive spheres (IECS) is accomplished by loading organohydrogel into the skeleton via “permeation and self‐assembly”. The resulting interpenetrating network produces a 3D continuous, conductive pathway and strong interface interaction with high‐density hydrogen bonding, thus exhibiting excellent strength (24.5 MPa), conductivity (14.82 S m −1 ), sensing performance (sensitivity of 16.64), and environmental stability. The physical structure (3D skeleton, interpenetrating network) and chemical interaction (interface interaction, salting‐out) achieve energy dissipation. Meanwhile, the sensitivity is enhanced by dual‐mode conduction, conductive sphere array, and deformation amplification induced by collagen fibers. Additionally, the strong bonding ability between glycerin and collagen fibers with water molecules provides anti‐freezing and moisture‐retention characteristics. Thus, the strategic synergy of compositional and structural design makes IECS a promising force‐sensing part of piezoresistive sensor for human movement, pulse frequency, cipher transmission, and pressure distribution. In short, IECS presents a multifunctional platform for the invention of high‐performance e‐skin with on‐demand property, which offers great application potential in wearable electronics.