Erectile dysfunction (ED) is a common and distressing complication in men with type 2 diabetes mellitus (T2DM), primarily caused by endothelial dysfunction, impaired nitric oxide signaling, and metabolic abnormalities. Phosphodiesterase-5 inhibitors such as tadalafil are widely prescribed for ED; however, their effectiveness may be reduced in diabetic patients due to underlying vascular damage. Dapagliflozin, a sodium–glucose co-transporter-2 (SGLT2) inhibitor used for glycemic control, has demonstrated additional benefits including improvement in endothelial function, blood pressure reduction, and enhanced vascular health. These effects suggest a potential supportive role of dapagliflozin in improving erectile function and augmenting the therapeutic response to tadalafil in diabetic individuals. Alongside therapeutic considerations, accurate and reliable analytical methods are essential for quality control and regulatory compliance of these drugs. This review provides a comprehensive overview of the physicochemical properties, pharmacological significance, and reported analytical methods for dapagliflozin and tadalafil, with emphasis on reverse-phase high-performance liquid chromatography (RP-HPLC). Various chromatographic conditions, validation parameters, and official pharmacopoeia methods are discussed. Overall, this review serves as a valuable reference for pharmaceutical analysts and researchers involved in method development and quality assessment of these clinically important agents.