Houttuynia cordata is a food and medicinal plant with high nutritive value. To explore the antioxidant and anti-diabetic activity, and major phytochemical composition of H. cordata water extract, the total content of phenolics, flavonoids, sugar, and protein of H. cordata extracts and its fraction, along with its antioxidant activity, α-glucosidase inhibitory, and anti-glycation ability were evaluated, and the chemical compositions of high bioactivity were identified by mass spectrometry technology. Results indicated that the ethyl acetate fraction of H. cordata water extract (EAF) had the highest total phenolics (440.3 mg GAE/g), total flavonoids (103.57 mg QUE/g), and total proteins (2.45 mg BSA/g) content, but it displayed the lowest total sugar content (11.32 mg Glu/g). Simultaneously, the EAF also showed the strongest α-glucosidase inhibitory, ABTS cationic radical scavenging ability, and DPPH radical scavenging ability with IC50 values of 232.63 μg/mL, 50.00 μg/mL, and 71.67 μg/mL, respectively. The α-glucosidase inhibition activity of EAF was 3.15 times higher than acarbose, followed by the n-butanol fraction of H. cordata water extract (nBuF). When the mass concentration of EAF was 4.0 mg/mL, the percentage inhibition of EAF on AGEs information was over 70%, the nBuF came second. Pearson correlation analysis implied that phenolics were the major compounds with excellent antioxidant and anti-diabetic activities. A total of 40 compounds were identified from EAF and nBuF by HPLC-QTOF-MS/MS. Phenolic acid, quercetin glycoside, and kaempferol glycoside were the main active components. Therefore, H. cordata has great application potential in the antioxidation and prevention of diabetes and its complications and has the value of a further study on antioxidant and anti-diabetes effects in vivo.
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