This study presents wet-responsive, shape-reconfigurable, and flexible hydrogel adhesives that exhibit strong adhesion under wet environments based on reversible interlocking between reconfigurable microhook arrays. The experimental investigation on the swelling behavior and structural characterization of the hydrogel microstructures reveal that the microhook arrays undergo anisotropic swelling and shape transformation upon contact with water. The adhesion between the interlocked microhook arrays is greatly enhanced under wet conditions because of the hydration-triggered shape reconfiguration of the hydrogel microstructures. Furthermore, wet adhesion monotonically increases with water-exposure time. A maximum adhesion force of ~79.9 N cm−2 in the shear direction is obtained with the hydrogel microhook array after 20 h of swelling, which is ~732.3% greater than that under dry conditions (i.e., ~9.6 N cm−2). A simple theoretical model is developed to describe the measured adhesion forces. The results are in good agreement with the experimental data.