This study investigated the use of eco-friendly novel formulations of deep eutectic solvents (DESs) with water in ultrasound-assisted extraction (UAE) of antioxidant compounds from six spices, comparing them to traditional ethanol-based solvents. Significant differences in antioxidant capacity (AC) determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP) assays, and total phenolic content (TPC) analysed using Folin-Ciocalteu (F-C) method were observed among the prepared extracts of spices. Regardless of the solvent used, clove extracts exhibited the highest antioxidant properties, whereas coriander presented the lowest values of AC and TPC. Choline chloride (ChCl)-based DES3 with propylene glycol (PG) as the hydrogen bond donor was more promising for effectively extracting antioxidants from the studied spices than ChCl-based DES1 and DES2 containing urea (U) and glycerol (Gly), respectively. Although DESs showed lower efficiency in this study, they represent a viable and environmentally sustainable approach for the extraction of bioactive compounds from spices. However, DES-based extracts can be recommended as potential sources of bioactive compounds and sustainable solvent systems for the plasticization and modification of active food packaging. This research offers valuable insights for the food, pharmaceutical, cosmetic, and spice industries, particularly for future developments in sustainable extraction techniques and potential applications in eco-friendly solutions and health-related areas.