Recording electrophysiological information such as brain neural signals is of great importance in health monitoring and disease diagnosis. However, foreign body response and performance loss over time are major challenges stemming from the chemomechanical mismatch between sensors and tissues. Herein, microgels are utilized as large crosslinking centers in hydrogel networks to modulate the tradeoff between modulus and fatigue resistance/stretchability for producing hydrogels that closely match chemomechanical properties of neural tissues. The hydrogels exhibit notably different characteristics compared to nanoparticles reinforced hydrogels. The hydrogels exhibit relatively low modulus, good stretchability, and outstanding fatigue resistance. It is demonstrated that the hydrogels are well suited for fashioning into wearable and implantable sensors that can obtain physiological pressure signals, record the local field potentials in rat brains, and transmit signals through the injured peripheral nerves of rats. The hydrogels exhibit good chemomechanical match to tissues, negligible foreign body response, and minimal signal attenuation over an extended time, and as such is successfully demonstrated for use as long-term implantable sensory devices. This work facilitates a deeper understanding of biohybrid interfaces, while also advancing the technical design concepts for implantable neural probes that efficiently obtain physiological information.

New materials and devices for bioelectronics have emerging applications in healthcare monitoring and disease diagnostics. Hydrogel‐based sensors face great challenges in achieving desirable synergistic performances including intrinsical electron conduction, bacterial resistance, anti‐swelling property, and adhesion to tissues. To address current bottlenecks, poly(Cu‐arylacetylide) derived hydrogels are developed for the first time that demonstrates all these above intriguing performances as a result of the special Cu‐arylacetylide backbone. The hydrogels show the capability of recording electrocardiogram (ECG), electromyogram, implantable epicardial ECG, and transmitting neural signals. Furthermore, the Cu (I) in polymer chains can be substituted by other metal ions such as Au (I), which can create numerous new materials with intriguing performances. This study not only creates a new research field of hydrogels but advances design concepts for implantable electrodes to record bio‐electron.