This study presents a novel strategy to regulate the surface properties of hydrogels, particularly their wettability and bioadhesion, without altering their chemical composition or bulk properties. The approach involves grafting hydrophobic polymeric chains onto mold substrates, which induces dynamic interactions with the hydrogel surface during gelation, leading to a reconfiguration of the hydrogel network. This reconfiguration results in a higher content of hydrophobic polymer backbones and reduced polar groups, transforming the hydrophilic surface into a hydrophobic one. The effectiveness of this method is demonstrated through experiments showing significantly enhanced bioadhesion and transdermal delivery compared to conventional hydrogels. Molecular dynamics simulations further elucidate the atomic-level details of this network reconfiguration. The findings provide valuable insights into the dynamic interactions between hydrogels and substrates and offer a versatile platform for customizing hydrogel surface properties for various applications.This study presents a novel strategy to regulate the surface properties of hydrogels, particularly their wettability and bioadhesion, without altering their chemical composition or bulk properties. The approach involves grafting hydrophobic polymeric chains onto mold substrates, which induces dynamic interactions with the hydrogel surface during gelation, leading to a reconfiguration of the hydrogel network. This reconfiguration results in a higher content of hydrophobic polymer backbones and reduced polar groups, transforming the hydrophilic surface into a hydrophobic one. The effectiveness of this method is demonstrated through experiments showing significantly enhanced bioadhesion and transdermal delivery compared to conventional hydrogels. Molecular dynamics simulations further elucidate the atomic-level details of this network reconfiguration. The findings provide valuable insights into the dynamic interactions between hydrogels and substrates and offer a versatile platform for customizing hydrogel surface properties for various applications.