Conductive hydrogels are essential for enabling long-term and reliable signal sensing in wearable electronics due to their tunable flexibility, stimulus responsiveness, and multimodal sensing integration. However, developing durable and dependable integrated hydrogel-based flexible devices has been challenging due to mismatched mechanical properties, limited water retention capability, and reduced flexibility. This work addresses these challenges by employing a tailored physical–chemical dual-crosslinking strategy to fabricate dynamically reversible organo-hydrogels with high performance. The resultant organo-hydrogels exhibit exceptional characteristics, including high stretchability (up to ∼495% strain), remarkable toughness (with tensile and compressive strengths of ∼1350 kPa and ∼9370 kPa, respectively), and outstanding transparency (∼90.3%). Moreover, they demonstrate excellent long-term water retention ability (>2424 h, >97%). Notably, the organo-hydrogel based sensor exhibits heightened sensitivity for monitoring physiological signals and motions. Furthermore, our integrated wireless wearable sensing system efficiently captures and transmits various human physiological signals and motion information in real-time. This research advances the development of customized devices utilizing functional organo-hydrogel materials, making contributions to fulfilling the increasing demand for high-performance wireless wearable sensing.