<p>Valsartan and labetalol are the drugs that belong to the class of antihypertensive drugs, angiotensin II receptors. A simple, less time-consuming, cost-effective, and green first-order derivative approach is developed for the effective and simultaneous detection of valsartan and labetalol. The first-order approach is well known for the estimation of mixed drugs. The present method is validated as per the recommendations of the ICH guidelines (ICH Q2R1). Validation parameters include linearity that contains r² values 0.9945 and 0.9967, respectively, for valsartan and labetalol. For the intraday and interday precision study, the assay value was found at 99.86 and 101.45%, and percentage recovery was achieved at 100.45 and 99.78%, respectively, for valsartan and labetalol. Based on the accuracy study the percentage recovery of valsartan was between 98.14 and 101.48%, and for labetalol, it was between 101.39 and 101.38%. The percentage recovery of robustness study found for valsartan and labetalol was between 98 and 102%. The limit of detection found for labetalol was 1.16 μg/mL and for valsartan it was 0.9 μg/mL. The quantification limit was achieved up to 3.52 and 2.72 μg/mL for valsartan and labetalol, respectively. Furthermore, the analytical greenness of the method was confirmed twice by utilizing the AGREE and GAPI greenness checker tools. Moreover, the method was applied to the estimation of the combined drug with the same medicinal applications in forensic science.</p>