The present study aimed to develop and validate a simple, precise, accurate, and robust RP-HPLC method for the simultaneous estimation of Metronidazole and Ciprofloxacin in tablet dosage forms. Chromatographic separation was achieved using an Inertsil ODS C18 column (250 × 4.6 mm, 5 μm) with a mobile phase consisting of Acetonitrile:Methanol:Water (50:30:20, v/v/v) at a flow rate of 1.0 mL/min under isocratic conditions. Detection was carried out at 250 nm. The method exhibited excellent linearity over concentration ranges of 20–60 μg/mL for Ciprofloxacin and 50–150 μg/mL for Metronidazole, with correlation coefficients greater than 0.999. The developed method was validated according to ICH guidelines for specificity, linearity, accuracy, precision, robustness, ruggedness, LOD, and LOQ. Recovery studies demonstrated excellent accuracy with recoveries ranging from 99% to 101%, while precision studies showed %RSD values below 2%. Accelerated stability studies confirmed the stability-indicating nature of the method, with no significant degradation observed under storage conditions of 40 ± 2°C/75 ± 5% RH for three months. The validated method was successfully applied to the assay of marketed Ciprodiazole tablets, yielding assay values of 97.31% for Ciprofloxacin and 98.43% for Metronidazole. The results demonstrated that the developed RP-HPLC method is reliable, sensitive, and suitable for routine quality control and stability analysis of combined tablet formulations containing Metronidazole and Ciprofloxacin.