Many studies have shown there is a close relationship between metal homeostasis disruption and Alzheimer's disease(AD), but the mechanism needs to be discussed. Recent progresses about these studies are reviewed especially the results in author's laboratory are discussed. Iron and copper homeostasis disruption, oxidative stress，β-amyloid (Aβ), amyloid precursor protein (APP), iron regulatory protein (IRP) and divalent metal transporter 1(DMT1) are discussed in detail. We suggested that the overload of iron and copper might have closer relationship with the oxidative stress damage in the later phase in AD and the deficiency of iron and copper might have closer relationship with the early initiation of AD. The protective effects of natural antioxidant against AD through regulating iron and copper homeostasis disruption and oxidative stress are also discussed. This review may be useful for further research and prevention and therapy of AD.