Display omitted •Antioxidant, neuroprotective and cardioprotective effects of two artichoke varieties.•Romanesco Siciliano showed highest antioxidant and anti-acetylcholinesterase capacities.•ex vivo-in vitro fecal fermentation model as tool to evaluate the food bioactives cardioprotective activities.•Romanesco Siciliano artichoke inhibited choline-d9 utilization and TMA-d9 production. The chemical composition and in vitrobiological activities of two globe artichoke varieties, Romanesco Siciliano (RS) and Spinoso Sardo (SS), were studied for their antioxidant activity and potential effects against age-related diseases. The globe artichoke extracts were subjected to three antioxidant activity tests, DPPH, ABTS and FRAP, and to the acetylcholinesterase neuro-related assay. The potential artichoke cardioprotective capacity was investigated by evaluating the inhibition of choline-d9 conversion into proatherogenic trimethylamine-d9 (TMA-d9), in an ex vivo-in vitro fecal fermentation model. In both globe artichoke varieties, the polyphenols profile was similar with chlorogenic and di-caffeoylquinic acids as the main polyphenols identified, although the amount changed with the variety (RS: 108.5; SS: 64.8 mg polyphenols/g DW). The RS sample gave the highest values of antioxidant and anti-acetylcholinesterase activities and mostly inhibited choline-d9 utilization (+28.0 % choline-d9 Area Under the Curve (AUC) compared to control), and TMA-d9 production (-31.9 % TMA-d9 AUC compared to control). All the reported results demonstrated that globe artichoke may provide potential cardioprotective, neuroprotective and antioxidant effects.