Postoperative adhesions (PAs) are a common complication after intraperitoneal surgery. Hydrogels are a physical barrier that prevents peritoneal adhesions, but their efficacy is still controversial. In this study, Laponites, a layered two-dimensional nanoscale, is incorporated into zwitterionic hydrogel (pSBLA) to enhanced biocompatibility and bioactivity to develop a nanocomposite for rapid prevention of postoperative and recurrent adhesion. The anisotropic distribution of charges in laponites results in strong hydrogen bonding and electrostatic repulsion in aqueous solutions and enables hydrogen bonding between amphiphilic ions, thereby enhancing the mechanical properties of hydrogels. The pSBLA hydrogels also possess a series of characters for an ideal anti-adhesion material, including resistance to adhesion against fibrinogen, proteins as well as cells. The mechanism underlying the extraordinary hydration of pSBLA is elucidated in this study using molecular dynamic simulations. In addition, pSBLA hydrogel is shown to represent a major advancement in anti-adhesion efficacy by completely and reliably preventing postoperative and recurrent adhesions after adhesiolysis in rat models. Furthermore, mechanistic explorations revealed that pSBLA hydrogel inhibits inflammatory responses and resists fibrosis by regulating the transforming growth factor-β/Smad signal pathway. Therefore, the pSBLA hydrogel has considerable potential for preventing post-operative adhesions in clinical settings.