Artichoke (Cynara scolymus L.) is a perennial plant belonging to the Asteraceae family originating from the Mediterranean region. In Vietnam, there are some varieties of artichoke which are extensively cultivated and propagated in highland areas, however, there have been limited detailed scientific publications on the chemical composition and biological activity of artichoke grown in Vietnam. Therefore, this study provides a detailed description of the extraction, isolation, and structural determination of 20 natural secondary metabolites present in harvested artichoke. The antioxidant activity of the extract and the 9 isolated compounds are tested in 1,1-diphenyl-2-picrylhydrazyl radical scavenging and ex vivo malondialdehyde model. Among the selected compounds, 1-caffeoylquinic acid, 3-caffeoylquinic acid, chlorogenic acid, 4-caffeoylquinic acid, cynarin, 1,5-dicaffeoylquinic acid, 4,5-di-caffeoylquinic acid, cynaroside, and scolymoside exhibited strong radical scavenging activity with IC50 values ranging from 5.7 to 61.6 µM. In the malondialdehyde assay, 1,3-dicaffeoylquinic acid (or cynarin) showed the strongest activity with an IC50 value of 24.7 µM, followed by 1,5-di-caffeoylquinic acid (66.8 µM), and 4,5-di-caffeoylquinic acid (127.3 µM). This outcome contributes to establishing a database on the phytochemical and antioxidant activity of the Vietnamese artichoke.