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Aims The peptidyl‐prolyl cis/trans isomerase, Pin1, has a protective role in age‐related neurodegeneration by targeting different phosphorylation sites of tau and the key proteins required to produce Amyloid‐β, which are the well‐known molecular signatures of Alzheimer's disease (AD) neuropathology. The direct interaction of miR‐140‐5p with Pin1 mRNA and its inhibitory role in protein translation has been identified. The main purpose of this study was to investigate the role of miRNA‐140‐5p inhibition in promoting Pin1 expression and the therapeutic potential of the AntimiR‐140‐5p in the Aß oligomer (AßO)‐induced AD rat model. Methods Spatial learning and memory were assessed in the Morris water maze. RT‐PCR, western blot, and histological assays were performed on hippocampal samples at various time points after treatments. miRNA‐140‐5p inhibition enhanced Pin1 and ADAM10 mRNA expressions but has little effect on Pin1 protein level. Results The miRNA‐140‐5p inhibitor markedly ameliorated spatial learning and memory deficits induced by AßO, and concomitantly suppressed the mRNA expression of inflammatory mediators TNFα and IL‐1β, and phosphorylation of tau at three key sites (thr231, ser396, and ser404) as well as increased phosphorylated Ser473‐Akt. Conclusion According to our results, Antimir‐140‐mediated improvement of AβO‐induced neuronal injury and memory impairment in rats may provide an appropriate rationale for evaluating miR‐140‐5p inhibitors as a promising agent for the treatment of AD.