Asymmetrically adhesive hydrogel patch with robust wet tissue adhesion simultaneously anti-postoperative adhesion is essential for clinical applications in internal soft-tissue repair and postoperative anti-adhesion. Herein, inspired by the lubricative role of serosa and the underwater adhesion mechanism of mussels, an asymmetrically adhesive hydrogel Janus patch is developed with adhesion layer (AL) and anti-adhesion layer (anti-AL) through an in situ step-by-step polymerization process in the mold. The AL exhibits excellent adhesion to internal soft-tissues. In contrast, the anti-AL demonstrated ultralow fouling property against protein and fibroblasts, which hinders the early and advanced stages of development of the adhesion. Moreover, the Janus patch simultaneously promotes tissue regeneration via ROS clearance capability of catechol moieties in the AL. Results from in vivo experiments with rabbits and rats demonstrate that the AL strongly adheres to traumatized tissue, while the anti-AL surface demonstrate efficacy in preventing of post-abdominal surgery adhesions in contrast to clinical patches. Considering the advantages in terms of therapeutic efficacy and off the shelf, the Janus patch developed in this work presents a promise for preventing postoperative adhesions and promoting regeneration of internal tissue defects.