Cloperastine (1-[2-(p-chloro-alpha-phenylbenzyloxy) ethyl] piperidine) is a drug with an antihistaminic effect and central antitussive; it is a well-known anti-cough drug that plays an important rule against respiratory symptoms during the treatment of coronavirus disease 2019 (COVID-19). This study aimed to develop an accurate, simple, and sensitive validated reversed phase high-performance liquid chromatographic (HPLC) method for the determination of cloperastine fendizoate, as active substance simultaneously with the preservation additives methyl parahydroxybenzoic acid (methyl paraben) and propyl parahydroxybenzoic acid (propyl paraben) in its pure and pharmaceutical dosage. Analysis and quantitation were based on drug direct UV detection wavelength of 248 nm using an isocratic mobile phase consisting of acetonitrile as an organic solvent and phosphate buffered solution of pH 3.0. This method was developed on a reversed-phase ZORBAX ECLIPSE plus-C18 (4.6 × 250 mm, 5-µm) analytical column with a flow rate of 1.5 mL min-1 at a normal temperature of 25 °C. The separation of cloperastine fendizoate together with additives; methyl paraben and propyl paraben was achieved at 10.8, 3.7, 8.7 minutes, respectively. The developed method validation was performed following previously describe procedures according to the International Conference on Harmonization (ICH) guidelines to confirm its linearity, precision, and accuracy. Finally, using simple, common available analytical tools, separation of analytes achieved within 13 min. Robustness of analytical method confirmed that the proposed method can tolerate small variations on applying different method parameters.