To investigate the efficacy and safety of olanzapine, aripiprazole, and risperidone in the treatment of mental and behavioral symptoms of Alzheimer’s Disease. A retrospective analysis was performed on the clinical data of 126 patients with Alzheimer’s Disease from February 2018 to February 2020. The patients were divided into group A (aripiprazole, n=44), group B (olanzapine, n=42) and group C (risperidone, n=40) based on the treatment method. Remarkably differences at different time points among the three groups were observed (P<0.05). Significant differences in the Positive and Negative Syndrome Scale scores of different time points and cross-group comparison among the three groups were detected (P<0.05). The time-point comparison of BEHAVE-AD scores among the three groups indicated a remarkable difference (P<0.05). After 4 weeks of treatment, the Positive and Negative Syndrome Scale and BEHAVE-AD scores of group A were lower than those of groups B and C (P<0.05). The total incidence of adverse reactions in group A was remarkably lower than in groups B and C (P<0.05). Olanzapine, aripiprazole and risperidone are effective in treating Alzheimer's disease and aripiprazole, with a better safety profile and fewer adverse reactions, is more suitable for elderly patients.