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Copper oxide nanoparticles (CuONPs) can be an inexpensive alternative to silver and gold nanoparticles. However, work toward the sustainable synthesis of colloidal CuONPs is limited. This work establishes a simple microwave-assisted synthesis for colloidally stabilized, antibacterial CuONPs synthesized from glucose, starch and CuCl₂. Optimization using response surface methodology with central composite design enhanced the sustainability of CuONP production process. The antibacterial properties of CuONPs were tested against gram-positive, gram-negative, spore-forming and methicillin-resistant bacteria. Transmission electron microscopy (TEM) and X-ray diffraction (XRD) were used for elemental and morphological characterization. Bandgap, yield and production were determined by spectrophotometry and a cupric ion selective probe. CuONP formation was verified by the presence of a maximum …