Metal oxide nanoparticles (MONPs) are utilized in many arenas. They can be formulated via various methods for example eco-friendly synthesis, this method contains infinite accession to create MONPs with required properties. Most plants have features as supportable and renewable providers compared with enzymes and microbes, as they have the ability to collect nearly 75% of the energy of light and transform it into energy of chemical, which play fundamental roles in the manufacture of nanoparticles due to containing sugars and antioxidants. In this research green method was applied for the preparation of a novel type of coated wire electrodes for potentiometric determination of ciprofloxacin hydrochloride in pure and pharmaceutical commercial based on metal oxide nanoparticles (ZnO NPs) were synthesized chemical and green sources, leaves extract of Myrtus communis and Mentha, respectively. The electro-active material ciprofloxacin-molybdophosphoric acid (CFX-PM) was made via mixing CFX with molybdophosphoric acid (PM) with used n-Di butyl phthalate (DBP) as a plasticizer. More sensitive sensors were given a Nernst slope equal to 57.89, 58.71, and 59.69 mVdecade-1 with a linear range around 9.0×10^-9-1.0×10^-2, 1.0×10^-9-1.0×10^-2 and 1.5×10^-9-1.0×10^-2 mol.L^-1 and the limit of detections were 7.3×10^-10, 5.0×10^-10 and 1.2×10^-10 mol.L^-1 with correlation coefficients were 0.9995, 0.9994, and 0.9991 with lifetime equal to 35,36 and 41days for ZnO NPs, ZnO NPs with leaves extract of  Myrtus communis and Mentha coated wire electrodes, respectively. The results displayed excellent selectivity and sensitivity of the improved coated wire electrodes with nanometal oxide for the determination of the ciprofloxacin hydrochloride in original samples and marketable formula.