Natural deep eutectic solvents (NADES) are a new alternative to toxic organic solvents. Their constituents are primary metabolites, non-toxic, biocompatible and sustainable. In this study five selected NADES were applied for the extraction of propolis as an alternative to water-alcohol mixtures, and the antimicrobial and antioxidant potential of the extracts were studied. The extraction efficiency was evaluated by measuring the extracted total phenolics, and total flavones and flavonols. The qualitative composition was studied by GC-MS. Best results were achieved using citric acid – 1,2-propanediol 1:4 (CAPD), it extracted the same amount of phenolics and only somewhat lower amount of flavonoids than 70% ethanol. The GC-MS analysis confirmed that the major propolis constituents: pinocembrin, chrysin, galangin, CAPE, chemical markers of poplar type propolis and well-known bioactive compounds, are major constituents of all studied NADES extracts. Their antimicrobial and radical scavenging activity was of the same order of magnitude as the conventional ethanol extract, the best antibacterial activity was obtained with CAPD, much better that the one of the ethanol extract. The best radical scavenging activity (DPPH) was observed for choline chloride – glucose 5:2 with 30% water. Our results confirm the potential of NADESs for extraction of bioactive constituents from propolis and suggest that NADES can improve the effects of extracted bioactive substances. Further studies are needed to clarify in detail the influence of the NADES on the bioactivity of the extracts, and their potential to be used in the pharmaceutical and food industry.