The Food and Drug Administration (FDA) authorized the administration of ritonavir (RIT)-boosted nirmatrelvir (NMV) on May 25, 2023, for the treatment of mild to moderate COVID-19 in patients who are at high risk of developing severe COVID-19. In accordance with sustainability and environmental friendliness, simple, eco-friendly, and sustainable spectrophotometric methods were established for concurrently estimating RIT and NMV in newly launched copackaged pills. The suggested solutions for resolving the spectral overlap between RIT and NMV involve the following mathematical methods: the first derivative method (1D), second derivative method (2D), and dual-wavelength zero-order method (DWZ). When ethanol was used as a green dilution solvent, the linearity range was adjusted (10–250 µg/mL) for both drugs. The procedures resulted in a high correlation coefficient (not less than 0.9996) and satisfactory levels of detection and quantification. Additionally, method validation was performed in accordance with International Council for Harmonization norms. Moreover, a detailed ecological and sustainability evaluation protocol was established to confirm the greenness and whiteness of the methods. Finally, the proposed method, along with previously reported methods for analysing NMV and RIT, were reviewed analytically and ecologically.