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Artichoke (Cynara cardunculus (L.) subsp. scolymus Hayek) is an important component of the Mediterranean diet, and a good source of health-promoting compounds, including polyphenols. The main phenolic compounds of artichoke are 5-O-caffeoylquinic acid (chlorogenic acid), and 3,5-O-, 1,5-O-dicaffeoylquinic acids and its beneficial effects are linked to their antioxidant activity that can be affected by their stability under gastro-intestinal conditions, during digestion. This study aimed to assess the antioxidant activity induced by artichoke head extract, and its main individual polyphenols, on a stimulated HT-29 cell line, using a DCFH-DA probe. In addition, influences of in vitro digestion on artichoke head and its individual polyphenols towards antioxidant activity, were tested. Artichoke extract showed higher antioxidant activity than the individual polyphenols, even after in vitro gastro-intestinal digestion. In addition, in vitro digestion did not modify the antioxidant activity of artichoke polyphenols, except for 1,5-O-dicaffeoylquinic acid, which proved to be the least active.