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The development of innovative antimicrobial materials is crucial in thwarting infectious diseases caused by microbes, as drug-resistant pathogens are increasing in both number and capacity to detoxify the antimicrobial drugs used today. An ideal antimicrobial material should inhibit a wide variety of bacteria in a short period of time, be less or not toxic to normal cells, and the fabrication or synthesis process should be cheap and easy. We report a one-step microwave-assisted hydrothermal synthesis of mixed composite Cu<i>_x</i>Fe<i>_y</i>O<i>_z</i> (Fe₂O₃/Cu₂O/CuO/CuFe₂O) nanoparticles (NPs) as an excellent antimicrobial material. The 1 mg/mL Cu<i>_x</i>Fe<i>_y</i>O<i>_z</i> NPs with the composition 36% CuFeO₂, 28% Cu₂O and 36% Fe₂O₃ have a general antimicrobial activity greater than 5 log reduction within 4 h against nine important human pathogenic bacteria (including drug-resistant bacteria as well as Gram-positive and Gram-negative strains). For example, they induced a >9 log reduction in <i>Escherichia coli</i> B viability after 15 min of incubation, and an ~8 log reduction in multidrug-resistant <i>Klebsiella pneumoniae</i> after 4 h incubation. Cytotoxicity tests against mouse fibroblast cells showed about 74% viability when exposed to 1 mg/mL Cu<i>_x</i>Fe<i>_y</i>O<i>_z</i> NPs for 24 h, compared to the 20% viability for 1 mg/mL pure Cu₂O NPs synthesized by the same method. These results show that the Cu<i>_x</i>Fe<i>_y</i>O<i>_z</i> composite NPs are a highly efficient, low-toxicity and cheap antimicrobial material that has promising potential for applications in medical and food safety.