In the pursuit of sustainable pharmaceutical analysis, Green Analytical Chemistry emerges as a vital approach to protect both human health and the environment. This study focuses on a green analytical approach for the simultaneous evaluation of Domperidone (DP) and Pantoprazole (PP), two widely used gastrointestinal drugs with distinct mechanisms and therapeutic roles. A suite of advanced spectrophotometric techniques, including the Deconvoluted Fourier method (DF), the Dual Wavelength method (DW), and both First-Order Derivative (D1) and Second-Order Derivative (D2) methods, was developed for the simultaneous determination of DP and PP. The linearity ranges were found to be (1.0– 9.0) µg/mL for both drugs; this range applies to all the proposed methods. Accuracy and reliability were confirmed via the standard addition technique. Furthermore, the performance of the suggested approaches was statistically compared with that of previously reported HPLC methods, showing their efficiency, eco-friendliness, and practical applicability. The methods were applied to laboratory-prepared combinations with varying concentrations of the two drugs to evaluate selectivity, as well as to their commercially available dosage forms. These methods were rigorously assessed for their environmental sustainability using green analytical chemistry metrics: The Analytical Eco-Scale, the Modified Green Analytical Procedure Index (MoGAPI), the Analytical Green Star Area (AGSA), Carbon footprint (CaFRI), Blueness evaluation using BAGI tools, Click Analytical Chemistry Index (CACI) and the Multi-Color Assessment (MA)