Chlorhexidine (CHX)/β-cyclodextrin (β-CD) inclusion and chitosan nanoparticles containing bovine serum albumin (CS/BSA) were blended into chitosan acetic acid solution respectively or simultaneously to prepare a novel thermosensitive hydrogel dual sustained-release system. Rheological properties, release, cytocompatibility, and antibacterial activity were investigated. The results confirmed that CHX/β-CD and CS/BSA were well dispersed in the solution, and the rheological property of hydrogel was not affected. The system exhibited promising dual sustained release and cytocompatibility. Antibacterial results showed that CHX-loaded hydrogel had a desirable therapeutic effect on Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli).