This study fulfilled the preliminary research aims and proved that RP-HPLC could be used for the pharmaceutical analysis of Cefixime and Azithromycin in pharmaceutical formulations using UV detection. The medications belong to distinct classes. The proposed and verified approaches outperformed previously published methods in terms of sensitivity, selectivity, repeatability, stability, and recovery, all while exhibiting minor matrix effects. RP-HPLC has been shown to be an effective approach for the simultaneous measurement of azithromycin and cefixime.