A dynamic in vitro gastrointestinal model (GID) was used to evaluate the effect of high-pressure processing (HPP) and food matrix on bioaccessibility and antioxidant activity (AA) of onion flavonols. A dietary supplement of quercetin was also submitted to GID. HPP (400 MPa/25 degrees C/5 min) combined with freeze-drying produced a significant increase of major onion flavonols, Q-3,4'-DiGlu (5%), Q-4'-Glu (30%), Iso-3,4'-DiGlu (5%) and Q-3-Glu (14%). Onion flavonols concentration decreased gradually through GID. The most bioaccessible flavonols were quercetin-diglucosides (23-96%) and the less were quercetin-monoglucosides (5-23%) and quercetin-aglycone (6-10%). Although GID phases of HPP-onion presented higher total flavonol content (9-16%) than control-onion, the bioaccessibility of total flavonols in both samples were similar (similar to 17.63%) and significant higher than that of quercetin dietary supplement (0.028%). Then, onion matrix affected positively flavonol bioaccessibility. Significant positive correlations were found between total flavonol and AA determined by ABTS'+ and FRAP and between total TP-FC and DPPH. during GID. Published by Elsevier Ltd.