Abstract Green chemistry and white chemistry are two approaches to chemistry that prioritize sustainability and environmental protection. The pursuit of green chemistry is to develop chemical processes and products that decrease or stop the use and generation of dangerous materials. In contrast, white chemistry focuses on developing energy-efficient, sustainable chemical processes that produce minimal waste. Our study evaluated the environmental friendliness of the suggested approach, using eight greenness appraisal techniques, including analytical eco-scale, analytical method volume intensity, HPLC-environmental assessment tool, analytical method greenness score, analytical greenness, analytical greenness metric for sample preparation, green analytical procedure index, and complexgreen analytical procedure index, in addition to the unique metric blue applicability grade index of white chemistry. We have developed and validated a highly effective and reliable method for concurrently analyzing designated pharmaceutical medications characterized in metformin (MET) and empagliflozin (EMP) formulations, including their degraded products. This method is cost-effective, specific, and environmentally friendly, utilizing reversed-phase high-performance liquid chromatography with an XBridge BEH C8 column (150 mm × 4.6 mm, 5 μm) at a flow rate of 1.0 mL·min−1, an injection volume of 5.0 μL, a column oven temperature of 50°C, a wavelength of 224 nm, and a mobile phase comprised of phosphate buffer adjusted at pH 6.8 and acetonitrile in gradient mode. In the HPLC method, linearity has been achieved over the concentration range of 10–106 and 30–1,050 µg·mL−1 for EMP and MET, respectively, with correlation coefficients more than 0.999 and good recoveries within 98–102%. An assessment of the content uniformity of finished products confirmed that they met the declaration’s acceptance standards (85–115%). A comparative study has been successfully conducted on generic and reference products, demonstrating their similarity. The suggested approach was validated by adhering to international council for harmonisation criteria.