Nowadays the multifunctional approaches to kill oral bacteria based on various nanocomposites have made great progress against periodontal infections, while the material structure and its functional integration are still insufficient. Herein, this work proposes a therapeutic strategy of chemodynamical therapy (CDT) and photothermal therapy (PTT) in monocrystals to effectively enhance the synergistic treatment. The CuS/MnS@MnO 2 consisting of hexagonal CuS/MnS nano-twin-crystal with a shell layer of MnO 2 is developed. In this nanosystem, the purpose of synergistic treatment of periodontitis by combining PTT/CDT is achieved within a CuS/MnS monocrystal, where CuS serves to achieve photothermal conversion, dissipate the biofilm and transfer the heat in situ to the integrated MnS, thus promoting the Mn 2+ -mediated CDT process. Meanwhile, the CDT process can generate the highly toxic hydroxyl radical to destroy extracellular DNA by utilization of endogenous H 2 O 2 produced by Streptococci in the oral biofilm, cooperating with PTT to dissipate the bacterial biofilm. With the design of the outer shell of MnO 2 , the selective bacteria-killing can be realized by producing oxygen which can protect the periodontal non-pathogenic aerobic bacteria and threaten the survival of anaerobic pathogens. Therefore, such design via multipattern strategies to combat microorganisms would provide a bright prospect for the clinical treatment of bacterial infections.