Ranunculus macrophyllus Desf. is a lesser-known yet regularly used vegetable in Mediterranean folk diets for its nutritional and medicinal properties. There is a lack of scientific data on its nutritional value and functionality. Therefore, the aim of this study was to investigate the nutritional and the phytochemical composition and the effect of in vitro digestion on the antioxidant activity and on individual polyphenols from an ethyl acetate extract. The proximate composition analysis showed good amounts of carbohydrates (72.4% dry weight, dw) and crude proteins (15% dw), while mineral analysis showed considerable amounts of calcium, magnesium, iron and zinc among other elements. The lipidic fraction showed potential anti-thrombotic and anti-atherogenic potential with beta-linolenic acid (40.8%) and linoleic acid (16.9%) as major compounds. The ethyl acetate fraction showed good amounts of total polyphenols (235 mg GAE/100 g dw), flavonoids (43.5 mg QE/100 g dw) and flavonols (108 mg RE/100 g dw). The fraction showed good radical scavenging ability against 2,2-dipheny l-1-picrylhydrazyl (432 mg Trolox E/100 g dw), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (1240 mM Trolox E/100 g dw) and peroxyl radicals (14200 mM Trolox E/100 g dw) even after in vitro digestion. Caffeic and coumaric acids showed good bioaccessibility between 97 and 102% while catechin and luteolin had lower bioaccessibility ranging from 34.2 to 38.7%. R. macrophyllus Desf. was found to be a good source of nutritional and non nutritional bioactive compounds with good bioaccessibility, which make its application in food and pharmaceutical industries potentially beneficial.