In this study, the ketoconazole-conjugated zinc oxide (ZnO) nanoparticles were prepared in a single-step approach using dextrose as an intermediate compound. The physical parameters confirmed the drug conjugation with ZnO and their size was around 70-75 nm. The drug loading and drug release studies indicated that the -CHO group from the dextrose increase the drug loading up to 65% and their release kinetics were also studied. The anti-fungal studies indicated that the prepared nanoparticles exhibit strong anti-fungal activity and the minimum concentration needed is 10 mg/ml. The nanoparticles loaded semi-solid gel was prepared using carbopol, methylparaben, propyl paraben and propylene glycol. The penetration of the ketoconazole-conjugated nanoparticles was studied using the skin. The results indicated that the semi-solid gel preparations influenced the penetration and also favoured the accumulation into the skin membrane. The veterinary clinical studies indicated that the prepared gel is highly suitable for treatment of .