<p>Continuous health monitoring is essential for the management of cardiovascular and musculoskeletal disorders. Fiber-based electronics are widely recognized as ideal platforms for such applications, owing to their superior comfort and seamless integrability with textiles. However, advances in this field have been hindered by two major challenges: limitations in manufacturing processes and functional isolation among components. Here, a multifunctional ionic wrinkled fiber was developed by creating micro-wrinkles through a pre-stretch-coat-release strategy. This process was applied to a spandex fiber substrate coated with a composite electrode and an ionic thermoplastic polyurethane sensing layer. The micro-wrinkles act as mechanical signal amplifiers that work in synergy with an ionic capacitive sensing mechanism, endowing assembled devices with outstanding sensing performance—including a high pressure sensitivity of 2.8 kPa⁻¹ in an orthogonal cross-point architecture and a gauge factor of 1.79 as a single-fiber strain sensor. Additionally, the fiber exhibits efficient Joule heating, ultrahigh stretchability (&gt;450%), and excellent cyclic stability. To demonstrate its practical utility, two system-level platforms were constructed: a proactive closed-loop system for preventing carpal tunnel syndrome and a smart glove for enhanced human–machine interaction. This microstructuring strategy effectively enhances the sensitivity of fiber-based sensors, paving the way for next-generation health management systems that transition from passive monitoring to active, closed-loop therapeutic interventions.</p>