Natural products from plants were extracted and widely studied for their activities against many disease conditions. The selection of the extracting solvent is crucial to develop selective and effective methods for the extraction and isolation of target compounds in the plant matrices. Pharmacological properties of plant extracts and their bioactive principles are related to their excellent solubility, stability, and bioavailability when administered by different routes. This review aims to critically analyze natural deep eutectic solvents (NADES) as green solvents in their application to improve the extraction performance of plant metabolites in terms of their extractability besides the stability, bioactivity, solubility, and bioavailability. Herein, the opportunities for NADES to be used in pharmaceutical formulations development including plant metabolites-based nutraceuticals are discussed.