A simple, consistent and reasonable isocratic RP-high performance liquid chromatography (RP-HPLC) approach was developed and optimized for the concurrent determination of Ornidazole and Miconozole in bulk and tablet dosage forms. HPLC analysis illustrated satisfactory separation of Ornidazole and Miconozole and optimal resolution was attained with C18 column using methanol, 5mM Ammonium acetate in the ratio 40:60 v/v at pH 4.8 as the mobile phase and UV detection at 276 nm. A unique chromatogram and spectra for Ornidazole and Miconozole were able to be envisioned by developed methods, which are analogous to the sample results. The calibration curve's observed linearity for ORZ and MCZ at selected concentration range. Recovery studies investigated the approach's accuracy with percentage recovery ranges between 97.33% and 98.33%. The developed techniques were verified in terms of precision, accuracy and linearity. Quality by design (QbD) was employed to optimize the accurate ratio mobile phase, pH, flow rate and its impact on retention time and peak area. The validation outcomes met the acceptance criteria as per ICH recommendations and found to be reliable for the routine examination of drugs in therapeutic formulations. The developed methodology can be used for quantitative determination of Ornidazole and Miconozole combination in pharmaceutical formulations without the immersion of additional diluents or excipients.