Alzheimer's disease (AD) is a neurological disease. Dexmedetomidine (Dex) has been evidenced to exert neuroprotective effects on multiple neurological diseases, while the function of microRNA(miR)-214-5p on Dex-mediated AD progression via targeting the suppressor of zest 12 (SUZ12) remains unclear. This study obligates to investigate the regulatory functions of Dex, miR-214-5p and SUZ12 on AD.The expression of miR-214-5p and SUZ12 in APPswe/PS1dE9 mice (hereinafter referred to as AD mice) was examined. Thereafter, the AD mice were treated with Dex or increased miR-214-5p or reduced SUZ12 to determine the spatial memory ability, apoptosis of hippocampal neurons and the contents of serum inflammatory and oxidative stress factors of AD mice. Finally, the target relationship between miR-214-5p and SUZ12 was detected.MiR-214-5p was reduced and SUZ12 was elevated in AD mice. Dex administration reduced the apoptosis of hippocampal neurons, the contents of serum inflammatory factor and oxidative stress, and attenuated the cognitive impairment of AD mice accompanied by up-regulated miR-214-5p and down-regulated SUZ12, and the overexpression of miR-214-5p or reduction of SUZ12 could effectively enhance the Dex-treated effects on AD mice. MiR-214-5p targeted SUZ12.Dex may have a potential neuroprotective effect on AD via the miR-214-5p/SUZ12 axis. This study provides novel therapeutic targets for AD treatment.Copyright © 2021. Published by Elsevier Inc.