Review Natural deep eutectic solvents (NaDES) as an emerging technology for the valorisation of natural products and agro-food residues: a review Rub en F. Gonz alez-Laredo, 1 * V  ıctor Iv an Sayago-Monreal, 1 Martha Roc  ıo Moreno-Jim enez, 1 Nuria Elizabeth Rocha-Guzm an, 1 Jos e Alberto Gallegos-Infante, 1 Luisa Fernanda Landeros-Mac  ıas 1 & Martha Rosales-Castro 2 1 Tecnol ogico Nacional de M exico/Instituto Tecnol ogico de Durango, Blvd. Felipe Pescador 1830 Ote. Col. Nueva Vizcaya, 34080, Durango, Mexico 2 CIIDIR-IPN Unidad Durango, Sigma 119, Fracc. 20 de Noviembre II, 34220, Durango, Mexico (Received 26 April 2023; Accepted in revised form 8 August 2023) Summary A review paper on the natural deep eutectic solvents (NaDES) application to the extraction of bioactives from natural products and agri-food wastes is introduced. NaDES are eutectic mixtures of two or more natural compounds forming a liquid phase at room temperature based in hydrogen bond acceptors (qua- ternary amines, alcohols) and hydrogen bond donors (sugars, organic acids). NADES have unique prop- erties such as low toxicity, biodegradability and high solubility for a wide range of compounds. They represent a sustainable alternative to traditional organic solvents in a variety of applications, particularly metabolites extraction. Therefore, the status of NaDES is displayed in terms of their inspiration in nature, their preparation and physicochemical properties, as well as the extraction conditions for biologically important phytochemicals such as alkaloids, carotenoids, and phenolics (anthocyanins, isoflavonoids, and curcuminoids). Remarks on emerging technologies as well on therapeutic, hydrophilic, and hydrophobic NaDES systems are inserted. As NaDES can be easily prepared from natural and renewable sources, they are a promising green alternative in the food, nutraceutical, and pharmaceutical industries. Keywords Betaine, bioactives, choline chloride, deep eutectic solvents, extraction, hydrogen bond, phytochemicals, polyphenols. Introduction After the work of Abbott et al.(2004), the scientific community and the industry have been interested in natural deep eutectic solvents (NaDES) with the pur- pose of developing green extraction methods to obtain bioactive compounds from natural resources. During the last years, neoteric solvents, i.e., older known materials finding new applications as solvents, have been suggested as alternatives to toxic organic sol- vents. These include ionic liquids (IL), switchable sol- vents, bio-based solvents, and deep eutectic solvents (DES) (Singh et al., 2021). They are blends of certain substances that at specific proportions, result in a liq- uid with a lower melting point than the individual components. The extraction processes using DES from natural sources have led to highly effective, economi- cal, and truly eco-friendly approaches. When the DES are fabricated with natural and renewable compounds, such as alcohols, organic acids, sugars, or amino acids, they are recognised as NaDES (Choi et al., 2011). Besides being composed of abundant and common pri- mary metabolites, NaDES are a promising alternative to traditional organic solvents, as they are easily pre- pared, non-toxic, environmentally safe, biodegradable, sustainable, and relatively cheap. The novel combination and application of hydrogen bond acceptors (HBA) and hydrogen bond donors (HBD) of paired ingredients for the typical formula- tion of NaDES has been the goal of many recent reports (Fig. 1). The combination of quaternary ammonium salts with and HBD affords a mixture hav- ing lower melting points than the individual ingredi- ents, i.e., a type III eutectic solvents (Abbott et al., 2004). In the application of NaDES, a strong emphasis is towards sustainable extraction processes of agri-food residues and natural products such as aromatic and medicinal plants. Similarly, the alternative use of *Correspondent: E-mail: rubenfgl@itdurango.edu.mx International Journal of Food Science and Technology 2023 doi:10.1111/ijfs.16641 Ó 2023 Institute of Food, Science and Technology (IFSTTF). 1