One of the major challenges of nano-biotechnology is to engineer potent antimicrobial nanostructures (NS) with high biocompatibility. Keeping this in view, we have performed aqueous olive leaf extract mediated one pot facile synthesis of CuO-NS and CeO2-NS. Prepared NS were homogenous, less than 26 nm in size, and small crystallite units as revealed by scanning electron microscopy (SEM) and X-ray diffraction (XRD) analyses. Fourier transform infrared spectroscopy (FTIR) of CuO-NS and CeO2-NS showed typical Cu-O prints around 592–660 cm-1 and Ce-O bond vibrations at 453 cm-1. The successful capping of CuO-NS and CeO2-NS by compounds present in the plant extract was further validated by high performance liquid chromatography (HPLC) and thermal gravimetric analysis (TGA). Active phyto-chemicals from the leaf extract simultaneously acted as strong reducing as well as capping agent in the NS synthesis. NS engineered in the present study showed antibacterial potential at extremely low concentration against highly virulent multidrug-resistant (MDR) gram-negative strains (Escherichia coli, Enterobacter cloacae, Acinetobacter baumannii and Pseudomonas aeruginosa), alarmed by World Health Organization (WHO). Furthermore, CuO-NS and CeO2-NS did not show any cytotoxicity on HEK-293 cell lines and Brine shrimp larvae indicating that the NS green synthesized in the present study are biocompatible.