Flexible and stretchable hydrogels have drawn much attention as wearable sensors; however, most hydrogel sensors usually suffer from poor mechanical toughness and self-recovery, causing great limitation in their application for repeated sensing. Here, highly stretchable, tough, and antifatigue hydrogels are fabricated by incorporating nucleotide

(adenosine monophosphate, AMP) into hydrophobic association polyacrylamide (PAAm) networks. As a dynamic connected bridge, AMP significantly regulates mechanical

performances of hydrogels, wherein the anionic phosphate groups from AMP form ionic bonds with cationic micelles and the nucleobases of AMP bind with PAAm chains through hydrogen bonds. The noncovalent synergistic interactions in the hydrogel networks contribute to achieving fast self-recoverable and antifatigue behaviors at room temperature without any

external stimuli. More importantly, the nucleotide-regulated hydrogel presents durability and high sensitivity as pressure and strain sensors for the detection of various mechanical deformations. As a result, the hydrogels are successfully designed as wearable sensors for sensing various large and subtle human motions, including the bending of elbow, wrist, and finger and even the vibrations of the rib cage and larynx. It is envisioned that the nucleotide-regulated hydrogels would find broad applications in electric skins, medical monitoring, soft robotics, and flexible touch panels.