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The study evaluated the combined effects of drying methods (air drying [AD], hot AD [HAD], microwave drying [MD], and freeze‐drying [FD]) and ultrasonication parameters (sonication temperature [STemp]: 40, 50, and 60°C) and heating time (STime: 60 and 120 min) on natural deep eutectic solvent (NADES) extraction of phytochemicals from Amaranthus hybridus stem. Increasing the STemp increased the extraction yield (ECY) of the phytochemicals for all drying methods but increase in the heating time reduced the ECY slightly. MD combined with 60°C ST showed the highest ECY (53%), whereas HAD combined with 40°C ST had the lowest ECY (18%). At 60 min heating time, increasing the ST from 40 to 50°C increased the total phenolic content (TPC) in the extract for most drying methods except MD, and a sonication time of 120 min showed a slightly higher TPC, especially for MD samples. At 60 min sonication, total flavonoid content (TFC, 800 mgQE/g) was highest for AD plus 50°C ST and lowest for AD combined with 60°C (100 mgQE/g), whereas for 120 min sonication, MD and AD with 50°C showed the highest TFC (690 mgQE/g). FD retained better some of the vitamins (thiamine, riboflavin, niacin) but MD retained better vitamin C. The antioxidant capacity was not so much different among the drying methods except for FD, which showed lower values. These results provide a theoretical basis for the synergistic applications of drying and ultrasonication during NADES extraction of phytochemicals from Amaranthus hybridus. [ABSTRACT FROM AUTHOR]