Pharmaceutical quality control products (QC) demand quick, sensitive, and cost-effective methods to ensure high production at a low cost. Green analytical methods are also becoming more common in pharmaceutical research to cut down on the amount of waste that goes into the environment. Meclizine hydrochloride (MZH) and pyridoxine hydrochloride (PYH) are reported to be excellent for calming down COVID-19. As a result, the amount of MZH and PYH manufactured by multinational pharmaceutical organizations has increased considerably during the last several months. The present work proposes three environmentally friendly, straightforward, and sensitive spectrophotometric procedures for quantification of MZH in the presence of PYH in a pure and marketable formulations. The approaches under examination include ratio subtraction (RSM), induced dual wavelength (IDW), and Fourier self-deconvolution (FSD). PYH, on the other hand, was directly quantified at 290 nm. For both drugs, the procedures follow Beer’s law in the range of (5–50 µg/mL). The RSM, IDW, and FSD methods, as well as the zero-order approach for PYH, have all been verified in accordance with ICH standards. The ecological value of established methodologies was determined using four distinct ways: the national environmental methods index (NEMI), the analytical Eco-scale, the Analytical Greenness Metric (AGREE), and the green analytical process index (GAPI). Comparing the findings to those of the previously described spectrophotometric technique, no major changes were identified.