The development of functional hydrogel dressings with robust mechanical properties has posed a significant challenge in expediting the healing process of MRSA-infected wounds. To address this, a composite hydrogel, comprising carboxylated soybean cellulose nanocrystals (CNCs), poly(N-isopropyl acrylamide) (PNIPAM), dimethyl diallyl ammonium chloride (PDADMAC), and kaolin (CN/P-K) was synthesized. CNCs served to stabilize the interpenetrating polymer networks of PNIPAM and PDADMAC through hydrogen bonding and electrostatic interactions, respectively, while the kaolin interlayer improved the material toughness. This composite hydrogel exhibited desirable temperature sensitivity with a lower critical solution temperature of 36 °C, antibacterial properties, and mechanical strength, making it more suitable for drug release on wound surfaces. In vitro assays confirmed the biocompatibility, blood compatibility, increased coagulation ability, and antibacterial activity of the CN/P-K hydrogel. In vivo studies demonstrated that the CN/P-K hydrogel achieved a greater healing rate (>
99 %) on MRSA-infected wounds than commercial cationic hydrogels on the 12th day, promoting the inhibition of MRSA. In summary, a novel approach for developing interpenetrating hydrogels based on physical-chemical cross-linking was proposed, with this innovative hydrogel showing promise as a versatile drug carrier for wound dressings.