In this study, a green and effective extraction method was proposed to extract two main compounds, ginsenosides and polysaccharides, from American ginseng by combining deep eutectic solvents (DESs) with aqueous two-phase systems. The factors of type of DESs, water content in DESs, the solid–liquid ratio, extraction temperature, and extraction time were studied in the solid–liquid extraction. Then, the aqueous two-phase system (DESs-ethylene oxide–propylene oxide (EOPO)) and salty solution exchange (EOPO-salty solution) was applied for the purification of polysaccharides. The content of the polysaccharides and ginsenosides were analyzed by the anthrone–sulfuric acid method and HPLC method, which showed that the extraction efficiency of deep eutectic solvents (DESs) was better than conventional methods. Moreover, the antioxidant activities of ginseng polysaccharides and their cytotoxicity were further assayed. The advantages of the current study are that, throughout the whole extraction process, we avoided the usage of an organic reagent. Furthermore, the separated green solvent DESs and EOPO could be recovered and reused for a next cycle. Thus, this study proposed a new, green and recyclable extraction method for extracting ginsenosides and polysaccharides from American ginseng.