<p>The citrus industry generates ≈ 50% of byproducts (peel, seeds, pomace) that are rich in polyphenols, flavonoids, terpenoids, and pectins. These bioactives are typically recovered using conventional organic solvents, but these solvents are often toxic, poorly selective, energy-intensive, and generate substantial waste, so there is a clear need for more sustainable options. This review synthesizes the potential of deep eutectic solvents (DES) and their natural variants ((Na)DES) for valorizing citrus residues in the context of a biorefinery. It outlines fundamental aspects and key properties (e.g., polarity, viscosity, and low volatility), classifications, and highlights type III systems (ChCl-based) for their performance-to-cost balance. It also analyzes how coupling with process-intensification technologies (UAE, MAE, PLE) can increase yield and selectivity in the recovery of phenolics and flavonoids (e.g., hesperidin and PMFs), pectin with improved functional attributes (Mw, emulsification), and volatiles (essential oils), through selective fractionation and deterpenation. This approach facilitates co-recovery in a single process train. Compared to hydroethanolic extraction, (Na)DES reduces processing times and solvent consumption and aligns better with the principles of green chemistry. Key scale-up bottlenecks, however, exist in high viscosity, solvent recovery/recycling, and evidence of mixture-level safety (residuals/migration, materials compatibility). Proposed mitigation measures include incorporating water as a third component, operating in continuous mode at moderate temperatures, and utilizing low-energy separations (anti-solvents, membranes, CO₂-switchable DES). Future priorities will center on predictive solvent design (COSMO, QSPR, ML), analytical/toxicological standardization, and comparative TEA/LCA to consolidate industrial adoption across agri-food sector value chains.</p> Graphical abstract <p></p>