Abstract: Objective To systematically evaluate the efficacy and safety of olanzapine combined with donepezil on the treatment of Alzheimer’s disease. Methods The databases PubMed, EMbase, The CochraneLibrary, CNKI, VIP and WanFang Data were searched by computar, and randomized controlled trials (RCTs) about olanzapine with donepezil treatment for Alzheimer’s disease from inception to September 2017 were collected. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.3 software . Results A total of 6 literatures of quality evaluation were selected. Treatment program of olanzapine with donepezil could significantly increase the total efficiency and MMSE score of patients with Alzheimer’s disease than that of alone olanzapine treatment, and the difference was statistically significant (P < 0.05). Conclusion The olanzapine and donepezil can improve the curative effect of elderly patients with Alzheimer’s disease.