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Nanoparticles of zinc oxide (ZnO NPs), propolis, and the ZnO–propolis composite (ZnO-P NCs) have been synthesized using a biomimetic approach. Zeta potential analysis and Fourier-transform infrared spectroscopy (FT-IR) proved the formation and stability of nanomaterials. Findings using X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), EDX-imaging, and transmission electron microscopy (TEM) demonstrated that the particle size of ZnO-P NCs was 9.70 nm. The antioxidant (DPPH radical scavenging) activity of synthesized nanomaterials was investigated. IC50 values of zinc oxide, propolis, and ZnO-P NCs nanoparticles were 2.75, 1.7, and 1.45 mg mL−1, respectively. In addition, their selectivity and anticancer activity for cancer cell lines (Hela and MCF-7) and human normal (W138) cell lines were investigated. ZnO-P NCs were highly effective against the cell line for breast cancer with an IC50 value of 18 µg/mL, indicating its anticancer-promising potent cytotoxicity in breast cancer treatment, and 23 µg/mL against cervical cancer. In addition, the higher observed safety, antioxidant, and anticancer activities for synthesized ZnO-P NCs confirmed the synergistic effect of this combination. It was obtained that the specific mechanisms underlying the synergy effect between zinc oxide nanoparticles and nanopropolis in their composite formulation varied depending on the preparation method, ratio, and concentration of the components. [ABSTRACT FROM AUTHOR]