Background: The study aims to integrate the Experiment Planning ( methodologies with High Performance Liquid Chromatography in the Reverse Phase (RP HPLC) for the development of an analytical method to estimate lobeglitazone. Method A DOE strategy was applied to maximize critical method parameters for RP HPLC, including mobile phase composition, flow rate, and column temperature. The method development was carried out using an analytical column Inspire with a C18 (150 × 4.6 mm,5 µ s tationary phase and acetonitrile containing mobile phase and potassium dihydrogen phosphate the procedure showed exceptional linearity range at wavelength of 24 0 nm with a correlation coefficient (R²) of 0.99 9 . The method was validated according to ICH guide lines, showing satisfactory results in terms of specificity, sensitivity, repeatability, and robustness. Results: The enhanced RP HPLC technique demonstrated high precision and accuracy in the estimation of lobeglitazone . The DOE approach enabled systematic optimization, resulting in a robust method with improved sensitivity and reduced analysis time. Conclusion: The integration of with DOE in RP HPLC method development offers a strategic approach to enhance analytical method performance. This stud y successfully established a reliable and efficient RP HPLC technique for determining lobeglitazone , which can be potentially applied in quality control and pharmacokinetic studies.