The flavonol content and anti-inflammatory and antioxidant activities of onion treated by high-pressure processing (HPP) and HPP combined with freeze-drying and pulverization (HPP-FD-P) were evaluated. Allium cepa L. var. cepa, 'Recas' was treated at T1 (200 MPa/25 °C/5 min), T2 (400 MPa/25 °C/5 min), and T3 (600 MPa/25 °C/5 min). After treatment, HP-treated and untreated samples were frozen (diced onion, HP-treated). Subsequently, part of the diced samples was freeze-dried and pulverized (pulverized onion, HP-treated and freeze-dried). Flavonol content and anti-inflammatory and antioxidant activities (hyaluronidase inhibiting activity, NO(•), ABTS(•+), and DPPH(•) scavenging capacity, ferric reducing antioxidant power, and antioxidative capacity by photochemiluminescence) were measured in nonhydrolyzed and hydrolyzed extracts. Hydrolysis was carried out in order to evaluate the effect of HPP and HPP-FD-P on both anti-inflammatory and antioxidant activities of extracts mainly containing aglycone forms. HPP-FD-P increased quercetin 3,4'-diglucoside, quercetin 4'-glucoside, quercetin 3-glucoside, and isorhamnetin 3,4'-diglucoside extractability. The present study suggests that HPP (especially treatment at 400 MPa) and HPP-FD-P may be of benefit for obtaining functional ingredients from onion, as suggested by increased NO(•) scavenging capacity and maintenance of the antioxidant activity mainly in hydrolyzed extracts.