The study’s primary goal is to create a novel ultra-high-performance liquid chromatography (UHPLC) technique that is exact, sensitive, and accurate. The primary goal is to calculate the dosages of montelukast and doxofylline in both pharmaceutical and bulk forms. A C18 (AGILENT) column was used to achieve the chromatographic separation of the drug and contaminants. The mobile phase consisted of 0.1% OPA and 57:43% v/v methanol (a pH of 4.2 with TEA). The detection was performed at 278 nm utilizing UV detection. According to the results, dinoxyline and montelukast were effectively eluted at retention durations of 3.523 and 4.918 minutes, respectively, with the flow rate adjusted at 1.0 mL/dinoxyline, with good resolution. The suggested method demonstrated linearity in the dosage ranging from 1 to 5 μg/mL of montelukast and 40 to 200 μg/mL of doxofylline. The range of recovery percentages for montelukast and doxofylline is 100.565 to 101.061%. The method’s validation was carried out in compliance with the specifications of the International Symposium on Harmonisation, resulting in good precision, sensitivity, accuracy, linearity, specificity, and robustness. In conclusion, the developed method successfully separates and estimates doxofylline and montelukast. Its application in routine analysis of these compounds in pharmaceutical formulations is viable and reliable.