Here we report hybrid antibacterial nanosheets (Zn–CuO@GO) where graphene oxide (GO) is decorated with zinc-doped copper dioxide (Zn–CuO) nanoparticles and applied as disinfectant agents to combat multidrug resistant bacterial strains from intensive care units (ICUs). The difference between different Zn–CuO decoration ratios was carefully evaluated and the results indicated when Zn–CuO was deposited onto GO at 4 : 1 weight ratio (w/w), the obtained Zn–CuO@GO exhibited the best dispersity, which was suitable as an antibacterial supplement for disinfectant. Importantly, the Zn–CuO@GO (4 : 1, w/w) based disinfectant could actively kill 100.0% multidrug bacteria strains within 10 min, including multidrug resistant (MDR) E. coli and methicillin resistant S. aureus (MRSA). Moreover, we measured the antibacterial activities of Zn–CuO@GO at other decoration ratios (i.e., 2 : 1 and 1 : 1, w/w) to study the effect of Zn–CuO decoration density on the antibiosis activity of Zn–CuO@GO. It was also found that decreased Zn–CuO deposition density not only caused the agglomerateion of Zn–CuO@GO nanosheets (largely due to the relatively increased GO ratio), but also extended their required function time to 30 min for complete bacterial killing. Taking Zn–CuO@GO (4 : 1, w/w) as the optimized antibacterial nanosheet, further TEM, SEM ad LCSM images revealed that Zn–CuO@GO functions via penetrating and wrapping into the cell wall, inducing bacterial sedimentation and cytoplasma leakage, which make them promising for next-generation disinfectant substitution.