Coreopsis tinctoria capitula (CTC) of the Compositae family has been used traditionally to treat various diseases in China, particularly type 2 diabetes mellitus (T2DM). This study evaluated the anti-lipid peroxidation, α-glucosidase and α-amylase inhibitory effects of CTC extracts, and analyzed its chemical composition by HPLC. Moreover, the antioxidant activity and protection effects of CTC extracts were investigated on high-fat/highsugar and streptozotocin-induced T2DM mice. In vitro study, the ethyl acetate extract (EAE) and butanol extract (BE) of CTC exhibited anti-lipid peroxidation (IC 50 : BHA > BE or EAE > ascorbic acid, p < 0.05) and α-glucosidase inhibitory activity (IC 50 : BE > EAE, p < 0.05). In vivo, the BE at the dose of 600 mg/kg was intragastrically given to T2DM mice, which exhibited a certain extent of repair and improvement of the levels of CAT, GSH, GSH-P X , SOD, as well as plasma biomarkers, compared with those in the model group (p < 0.05). These results demonstrated that CTC extracts have a positive effect to treat T2DM and it can be used for the treatment of T2DM in the future.