Dislocation of anti‐adhesion materials, non‐specific tissue adhesion, and the induction of secondary fibrinolysis disorders are the main challenges faced by postoperative anti‐adhesion materials. Herein, a self‐leveling transient unilateral adhesive hydrogel is custom‐designed to conquer these challenges with a theoretically calculated and dual‐step tailored gellan gum (GG) as the sole agent. First, the maximum gelation temperature of GG is lowered from 42–25 °C through controlled perturbation of intra‐ and inter‐molecular hydrogen bonds, which is achieved by employing the methacrylic anhydride as a “hydrogen bond's perturbator” to form methacrylate GG (MeGG). Second, the “self‐leveling” injectability and wound shape adaptably are endowed by the formation of borate‐diol complexed MeGG (BMeGG). Finally, the transient unilateral tissue‐adhesive hydrogel (BMeGG‐H) barrier is prepared through photo‐controlled cross‐linking of reactive alkenyl groups. This degradable hydrogel demonstrates favorable rheological properties, light‐controlled unilateral adhesion properties, biocompatibility, anti‐fibrin adhesion, and anti‐cell adhesion properties in vitro. Comprehensive regulation of the fibrinolysis balance toward non‐adhesion is conformed in a rat model after intra‐abdominal surgery via anti‐autoinflammatory response, intestinal wall integrity repair, and Tissue plasminogen activator (t‐PA) and plasminogen activator inhibitor‐1 (PAI‐1) balance adjustment. Notably, the 14th day anti‐adhesion effective rate is 100%, indicating its significant potential in clinical applications for postoperative anti‐adhesion.
