HypothesisFlexible and wearable hydrogel strain sensors have attracted significant attention for human activity monitoring and electronic skins. However, it remains a great challenge to develop an integrated hydrogel strain sensor showing intrinsic adhesive performances, tunable mechanical and high strain-sensitive properties. Marine mussels show a superior capacity to adhere to various substrates (including organic and inorganic), while polycaprolactone (PCL) can be easily modified into crosslinkers with different degrees of functionality (bi-, tri-, and quadri-functional groups) to control the crosslinking density. Therefore, the developed mussel-inspired 3,4-dihydroxyphenyl-l-alanine acrylamide–polycaprolactone (l-DMA–PCL) hydrogels could address these issues and serve as the potential wearable strain sensors for biomaterials and healthcare monitoring. Experimentsl-DMA monomers were successfully crosslinked by functionalized PCL (bi-, tri-, and quadri-functional) using UV light (wavelength ~ 365 nm) to prepare the l-DMA–PCL hydrogel. Adhesive behaviors, tunable mechanical properties and strain sensing performances of the l-DMA–PCL hydrogels were systematically studied. FindingsThe l-DMA–PCL hydrogel exhibited reversible adhesion to various material substrates (including steel, aluminum, ceramics, poly(ethylene terephthalate) (PET), wood, rubber, even for polypropylene (PP) and polytetrafluoroethylene (PTFE)) as well as skin. Moreover, the mechanical properties (stress: 50.2–72.4 KPa, strain: 700–1140%, Young’s modulus: 8.6–14.8 KPa, and toughness: 16.4–53.6 KJ/m3) of the hydrogels could be readily tuned by the modulation of functionality degree (bi-, tri-, and quadri-functional) of PCL. Intriguingly, the hydrogel-based wearable strain sensor showing high conductivity (0.0550 S/cm) and sensitive responses to both large (e.g., joint bending) and subtle human motions (e.g., frowning and speaking). Based on these achievements, this work provides new insights into the development of hydrogel with adhesiveness, controllable mechanical performance and high strain sensitivity as a flexible and wearable hydrogel strain sensors.