For the first time in the literature, the Analytical Quality by Design (AQbD) principles were applied to the development of a specific and simple quantitative proton nuclear magnetic resonance (1H-qNMR) method for quantitation of two antiviral drugs, molnupiravir (MOL) and favipiravir (FAV). This 1H-qNMR method was developed within the QbD framework, the new paradigm of quality recently outlined in the ICH Q14 guidelines. Basic principles of AQbD have been adapted starting with early risk assessment and identification of the analytical target profile (ATP), the analytical procedure attributes (APA) and the analytical procedure parameters (APPs). During the scouting phase, dimethyl sulfoxide-d6 (DMSO‑d6) was selected as the deuterated solvent and maleic acid as the internal standard. The quantitative determination was based on the selective proton signals from MOL's pyrimidine ring at 6.82 ppm (doublet) and FAV's hydroxyl group at 8.71 ppm (singlet), as well as a singlet signal from the IS at 6.24 ppm. A Box-Behnken Design was employed in response surface methodology to develop mathematical predictive models relating the APPs to the APAs followed by multicriteria- decision making with the aid of Derringer's desirability function. Finally, the method operable design regions (MODRs) were computed with the aid of Monte Carlo simulations and identified as the multidimensional combination of the APPs where the risk of failure to fulfill the requirements for the APAs was lower than 5 %. The most robust NMR conditions for MOL, with MODR intervals in brackets, were as follows: no. of scans of 72 (16–124.4), a relaxation delay of 19.8 s (1.2–40 s) and an acquisition time of 3.98 s (2.1–6 s). Similarly, for FAV NMR quantitation, the most robust conditions were found to be 72 scans (16–117.3), a relaxation delay of 19.8 s (1.4–40 s) and an acquisition time of 3.98 s (2.2–6 s). The developed method was validated in accordance with the recently endorsed ICH Q2R2 guidelines, and it exhibited detection limits of 1.04 and 0.88 mg mL−1, as well as quantitation limits of 3.45 and 2.95 mg mL−1 for MOL and FAV, respectively. The method was successfully applied to the analysis of the studied analytes in their pharmaceutical products, proving to be simple, fast, non-destructive, and accurate. Additionally, it can be considered an environmentally friendly alternative for quantitation and quality control analysis of pharmaceutical products. .