Metal-organic frameworks (MOFs) can be utilized as antibacterial agents due to their effective antibacterial activities. Four three-dimensional (3D) Cu-MOFs formulated as [Cu2(Glu)2(μ-L)]·x(H2O) (Glu is glutarate, and L is bpy = 4,4'-bipyridine (1), bpa = 1,2-bis(4-pyridyl)ethane (2), bpe = 1,2-bis(4-pyridyl)ethylene (3), and bpp = 1,2-bis(4-pyridyl)propane (4)) were synthesized by hydrothermal reactions or modified literature methods. Their solid-state structures were slightly modified to increase their hydrolytic stabilities in aqueous solution. Despite the seemingly sufficient void spaces in all the solvent-free MOFs, only the thermally activated form of MOF 2 displayed selective gas uptake ability for CO2 over N2 and H2. The antibacterial activities of the four Cu-MOFs, 1, 2, 3, and 4, were investigated by determining their minimal bactericidal concentration (MBC) values against five strains of bacteria, including E. coli, S. aureus, K. pneumonia, P. aeruginosa, and MRSA, which can be easily met in our daily surrounding environments. Although these Cu-MOFs were found to be structurally very stable in aqueous medium during antibacterial activity tests, they exhibited excellent antibacterial activities against all five kinds of bacteria, including Gram-positive bacteria (S. aureus and MRSA) and Gram-negative bacteria (E. coli, K. pneumonia, and P. aeruginosa), with very low MBCs. The robust 3D frameworks with surface active metal sites rather than the small amount of leached CuII ions may participate more strongly in inactivating various kinds of bacteria and reduce potential cytotoxicity mainly caused by leached metal ions.