OBJECTIVE： To separate and isolate total flavonoids from Dendrobium nobile leaves， and to investigate its anti-Alzheimer’s disease （AD） activity in vitro. METHODS： Total flavonoids were obtained by ultrasonic extraction method and extracted by chloroform， ethyl acetate and butyl alcohol after the obtained extract was dispersed with water. Qualitative analysis was carried out with color reaction and TLC. The content of total flavonoids in extracts was analyzed quantitatively by Aluminum nitrate-sodium nitrite method. Antioxidant activity of extract was investigated by DPPH radical scavenging assay； the inhibitory effect of each extract on Aβ42 protein aggregation was investigated by Thioflavin T assay. Metals （Cu2+， Fe3+， Zn2+） chelating property was studied by UV-vis spectrum scanning to investigate the anti-AD activity in vitro. RESULTS： The flavonoids were found in ethyl acetate， butyl alcohol and aqueous extracts， and their flavonoids contents were 0.03， 0.12， 0.05 mg/mL， respectively. IC50 of three extracts to DPPH free radicals were 0.021， 0.011， 0.013 mg/mL. Inhibitory rates of them to Aβ42 protein aggregation were 43.77％， 52.28％， 38.42％， respectively. Three extracts exerted metal chelating ability which was best in Cu2+. CONCLUSIONS： The total flavonoids from D. nobile leaves have good antioxidant activities， Aβ42 aggregation inhibitory activities and metal chelating activity， show certain anti-AD activity in vitro especially in butyl alcohol extract.