A rapid, straightforward, sensitive, efficient, and cost-effective reverse-phase high-performance liquid chromatographic method was employed to simultaneously determine Glucose, Sodium Citrate, and chloride in a drug solution for oral solution. Glucose, Sodium Citrate, and Chlorides are all listed in the USP monograph. While various assay methods are available, titrimetric methods are ineffective for trace-level quantification. Although IC, AAS, and ICP-MS offer high accuracy, they are expensive and often inaccessible to many testing facilities. When selecting methods, it’s crucial to consider quality control requirements and user-friendly techniques. A simple proprietary HPLC method has been developed to simultaneously quantify Chlorides, Glucose, and Sodium Citrate, with a shorter run time. The separation was carried out using a Shim-pack SCR-102(H) ion exclusion analytical column (7.9 mm x 300 mm, 7 µm) with a flow rate of 0.6 mL/min. The column compartment was kept at 40°C, and the injection volume was 10 µL, with detection at 200 nm. All measurements were performed in a 0.1% phosphoric acid solution. The analytical curves showed excellent linearity (r > 0.9999) within the concentration ranges of 0.74 to 1.74 mg/mL for Sodium Citrate (SC), 1.0 to 2.5 mg/mL for Sodium Chloride (SC), and 3.0 to 7.3 mg/mL for Glucose. The method was validated according to the guidelines of the International Conference on Harmonization (ICH Q2B) and USP<1225>. The method demonstrated precision, robustness, accuracy, and selectivity. During accelerated stability testing over six months, no significant variations were observed in organoleptic analysis and pH. Consequently, the developed method is considered suitable for routine quality control analyses, enabling the simultaneous determination of Sodium Citrate, Chloride, and Glucose in pharmaceutical formulations and solutions for oral rehydration.