Estrogen has been demonstrated to be involved in the development and progress of Alzheimer's disease. Numerous studies show the neuroprotective effects of estrogen, but the underlying mechanism remains unclear. Here, we discussed the neuroprotective effects of estrogen, particularly focusing on the energy metabolism related to improvement of glucose metabolism, regulation of the brain metabolism and enhancement of mitochondrial function. Application of estrogen or estrogen substitutes to maintain the nervous system function and to prevent and control Alzheimer's disease could be a fruitful field in future studies.