To investigate the differences in phenolic metabolites of foxtail millet from different regions and analyze their antioxidant mechanisms, this study used Jingu 21 foxtail millet as the research subject. Ultrasonic-assisted extraction technology, in vitro antioxidant assays, UPLC-MS/MS, and molecular docking were employed to systematically compare the phenolic metabolite characteristics of Jingu 21 foxtail millet from two regions in Shanxi. The results showed that the polyphenols in foxtail millet exhibited strong antioxidant capacity, with the millet from Longhua County (LC) demonstrating superior antioxidant properties compared to that from Anze County (AC). Through widely targeted metabolomics analysis, 186 phenolic metabolites with significant differences in content were identified between LC and AC, of which 124 differential polyphenols showed high accumulation in LC. These phenolic compounds were primarily flavonoids, including key flavonoid components such as Tricin, Homoplantaginin, and Iristectorin A. KEGG pathway enrichment analysis revealed that folate biosynthesis (ko00790) and phenylpropanoid biosynthesis (ko00940) were the most significantly different metabolic pathways. Molecular docking results with antioxidant-related key proteins indicated that differential polyphenols with binding energies ≤ -11 kJ/mol, such as Homoplantaginin, 6-Hydroxykaempferol-7-O-glucoside, Luteolin-3'-O-glucoside, and Cynaroside, were all highly accumulated in LC. In vitro experiments validated these findings for Homoplantaginin and Iristectorin A. A series of research results demonstrated that the antioxidant activity of phenolic metabolites in foxtail millet is influenced by regional environments, and the superior antioxidant capacity of LC compared to AC is mainly attributed to its abundant flavonoid content.