The production of plastic and the amount of waste plastic that enters the ecosystem increases every year. Synthetic plastics gradually break down into particles on the micro- and nano-scale in the environment. The micro- and nano-plastics pose a significant ecological threat by transporting toxic chemicals and causing inflammation and cellular damage when ingested; however, removal of those particles from water is challenging using conventional separation methods. Deep eutectic solvents (DES), a new class of solvents composed of hydrogen bond donors and acceptors, have been proposed as a cheaper alternative to ionic liquids. Hydrophobic DES derived from natural compounds (NADES) show promise as extractants in liquid–liquid extractions. This study investigated the extraction efficiency of micro- and nano-plastics including polyethylene terephthalate, polystyrene, and a bioplastic polylactic acid from fresh water and saltwater using three hydrophobic NADES. The extraction efficiencies fall in a range of 50–93% (maximum % extraction) while the extraction rates fall between 0.2 and 1.3 h (as indicated by the time to extract half the theoretical maximum). Molecular simulations show a correlation between the extraction efficiency and the association between the plastics and NADES molecules. This study demonstrates the potential of hydrophobic NADES as extractants for removal of different micro- and nano-plastic particles from aqueous solutions.