The global shift towards White and Green analytical chemistry (WAC, GAC) highlights a growing commitment to sustainability across scientific disciplines. The adoption of Analytical Quality by Design (AQbD) concepts in method development, as outlined in the International Council for Harmonisation (ICH) Q14 and Q2(R2) guidelines has widened the QbD domain over vast areas of analytical chemistry. In this context, this study presents the first integration of WAC and GAC principles into the AQbD workflow to develop a quasi-hydrophobic deep eutectic solvent-based dispersive liquid–liquid microextraction (Quasi-HDES-DLLME) method coupled with spectrophotometry for analyzing patent blue V (PBV) as a model analyte. To ensure sustainability, the Sample Preparation Metric of Sustainability (SPMS) tool and the Efficient, Valid, and Green (EVG) framework were incorporated into the AQbD workflow. Analytical Target Profile criteria were defined to address greenness and extraction efficiency, with early quality risk assessment (QRA) via an Ishikawa diagram identifying critical analytical procedure parameters (APPs). During the scouting phase, a DES (1:3 tetrabutylammonium chloride and n-decanoic acid) was selected as a green and efficient extraction solvent, with tetrahydrofuran (THF) as an aprotic solvent. Predictive models were generated using a Box-Behnken Design anticipating the effects of APPs on APAs. A second QRA, based on Monte Carlo simulations delineated the method operable design region (MODR), a zone ensuring less than 10 % risk of failure. This greenness-integrated, science-based approach visualized a 4D MODR, with the most robust working point identified as pH 4, DES volume 401.5 µL, THF volume 393.6 µL, and US time of 9 min. The method was validated according to ICH Q2(R2) guidelines, exhibiting quantitation and detection limits of 15 µg L−1 and 5 µg L−1, respectively. Its reliability and accuracy enabled successful PBV analysis in food and environmental samples, aligning with quality and sustainability standards.