Twelve Cu-based ternary (Cu-Me-S, Me = Fe, Sn, or Sb) and quaternary (Cu-Me-Sn-S, Me = Fe, Zn, or V) nanocrystalline sulfides are shown as perspective antibacterial materials here. They were prepared from elemental precursors by a one-step solvent-free mechanochemical synthesis in a 100 g batch using scalable eccentric vibratory ball milling. Most of the products have shown strong antibacterial activity against and bacteria. For instance, stannite CuFeSnS and mohite CuSnS were the most active against , whereas kesterite CuZnSnS and rhodostannite CuFeSnS exhibited the highest antibacterial activity against . In general, stannite has shown the best antibacterial properties out of all the studied samples. Five out of twelve products have been prepared using mechanochemical synthesis for the first time in a scalable fashion here. The presented synthetic approach is a promising alternative to traditional syntheses of nanomaterials suitable for biological applications and shows ternary and quaternary sulfides as potential candidates for the next-generation antibacterial agents.