Anesthesia-induced cognitive impairment is a recognized clinical phenomenon. The present study aimed to investigate the effect of microRNA-383 (miR-383) expression on propofol-induced learning and memory impairment. In total, 48 male Sprague-Dawley rats (weight, 250±10 g) were randomly divided into four groups (n=12 each): Control group, and three groups of rats that were anesthetized with propofol for 6 h and untreated (propofol model group), treated with a constructed lentivirus vector expressing miR-383 mimics (mimic + propofol group), or treated with miR-383 scramble (scramble + propofol group). The learning memory ability, hippocampal neuron apoptosis and expression of apoptosis-associated factors were detected using reverse transcription-quantitiative polymerase chain reaction and western blot analysis. Propofol treatment significantly reduced the relative mRNA and protein expression of miR-383, induced neuron apoptosis, upregulated the Bax/Bcl-2 ratio, downregulated the relative mRNA and protein expression levels of postsynaptic density protein 95 and cAMP-response element binding protein, and inactivated the phosphoinositide 3-kinase/protein kinase B signaling pathway. By contrast, miR-383 mimics significantly altered the propofol-induced dysregulation of the aforementioned factors. In conclusion, miR-383 mimic was able to repair propofol-induced cognitive impairment via protecting against hippocampal neuron apoptosis and dysregulation of related factors. The present study suggested that miR-383 may be used as a potential therapeutic target for the clinical treatment of cognitive impairment induced by propofol anesthesia.