A reliable and economical indirect spectrophotometric method was developed and validated for the quantitative determination of Imatinib Mesylate and Oseltamivir Phosphate in bulk drug samples and pharmaceutical dosage forms. The analytical procedure is based on the oxidation of the selected drugs with an accurately measured excess of ceric ammonium sulphate in a sulphuric acid medium. After completion of the oxidation reaction, the remaining unreacted oxidant was determined spectrophotometrically using Indigo Carmine as a chromogenic reagent. Experimental conditions affecting the analytical performance of the method, including acid concentration and reaction time, were carefully investigated and optimized to ensure maximum sensitivity and reproducibility. Under the optimized conditions, the method exhibited good adherence to Beer–Lambert’s law over the selected concentration range. Method validation was carried out according to International Council for Harmonisation (ICH) guidelines, evaluating parameters such as accuracy, precision, limit of detection (LOD), limit of quantification (LOQ), robustness, and ruggedness. Recovery studies demonstrated satisfactory accuracy and confirmed that commonly present pharmaceutical excipients did not interfere with the determination of the studied drugs. The proposed spectrophotometric procedure is simple, rapid, and cost-effective, and therefore can serve as a practical alternative to sophisticated instrumental techniques for routine quality control analysis of these pharmaceuticals.