Biocompatible hydrogels are highly valuable for wound management; however, improving their mechanical compatibility and achieving controlled drug release for dynamic wound treatment remain challenging. Inspired by skin structure and function, a novel mechanically-responsive hydrogel was developed using drug-loaded liposomes as structural units. The crosslinked hydrogel network was generated via free-radical polymerization of acrylamide, incorporating double-bond-functionalized liposomes as crosslinkers. Deformable liposomes endowed the hydrogel with improved mechanical properties and enabled controlled drug release in response to mechanical deformation. The rifampin-loaded mechanically-responsive hydrogel exhibited strong antimicrobial activity both in vitro and in vivo. In addition, anti-inflammatory effects and enhanced wound-healing properties were observed in dynamic wound environments. These findings indicate that mechanically-responsive skin-mimicking hydrogels offer a promising strategy for dynamic wound management.