One of prominent pathogen associated with skin and surgical wound infections is Staphylococcus aureus, a Gram-positive skin normal flora. Severe infected open wound with bacterial colonisation would require intravenous antibiotics therapies and tortuous hospitalization procedures. Emerging bactericidal agent with innovative nano-based green technology, may provide promising solution to tackle these issues. This study investigated the bactericidal potential of natural elements such as carbon and calcium decorated on ZnO–CuO nanocomposites synthesised from the medicinal plant Calotropis gigantea leaves. Dual-Ionic Honeycomb-like nanocomposites were produced at different calcination temperatures followed by characterization using x-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive spectroscopy (EDS), UV–Visible spectrophotometer, atomic absorption spectroscopy (AAS). The bactericidal efficiency of ZnO–CuO nanocomposites on S.aureus greatly improved with dual-ionic systems (i.e. Cu2+ and Zn2+) especially the low temperature-calcined with minimum inhibitory concentration of 2.5 mg/mL, minimum bactericidal concentration of 20 mg/mL and zone of inhibition (ZOI) of 6.83 ± 0.29 mm at concentration of 10 mg/mL. These observations suggested that different calcination temperatures of ZnO–CuO nanocomposites may be initiated by the divergent and controlled ion distribution on ‘honeycomb’ porous structure, which was the underlying mechanism of killing effect towards S. aureus. Findings from this study may contribute knowledge to the development of a synergistic bactericidal agent with that could efficiently overcome bacterial colonisation associated with skin and surgical wound infections.