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Oxidative stress and neuroinflammation are critical in the pathogenesis of neurodegenerative diseases. Extract of Coreopsis tinctoria Nutt. has been shown to ameliorate neurodegenerative diseases, potentially via inducing quinone oxidoreductase 1 (NQO1) and anti-neuroinflammation. The present study aimed to characterize the chemical profile and bioactive composition of the extract to identify the effective components responsible for the effects. Chromatography and spectra analysis yielded 26 constituents, including a new chalcone (compound 8 ). Bioassays showed that compounds 6 , 9 , 15 , 17 , 19 , 21 and 22 significantly inhibited production of nitric oxide (NO) in N9 cells induced by lipopolysaccharides (LPS). Meanwhile compounds 1 , 3 , 6 , 11 , 19 and 20 exhibited significant NQO1 inducing activities in Hepa 1c1c7 cells. These results suggest that extract of C. tinctoria Nutt. contains bioactive components attenuating the progress of neurodegenerative diseases, thus, a valuable functional food for the prevention of neurodegenerative diseases.