Background Emerging experimental evidence has shown that sirtuin 3 (SIRT3), which is a class III histone deacetylase, participates in the pathological process of Alzheimer’s disease (AD). However, data mining of current gene expression databases, such as Gene Expression Omnibus (GEO), has not been previously performed to determine whether SIRT3 expression is upregulated or downregulated in the brain tissues of AD patients. Material/Methods Eight RNA expression chip datasets of AD brains in the GEO database were selected, and GEO2R analysis was conducted to identify the differentially expressed genes (DEGs) between the AD and control groups. Furthermore, the SIRT3 mRNA levels between the AD and control groups and their relationships with the DEGs and diagnosis of AD were evaluated. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of both the AD-related DEGs and the SIRT3-related DEGs were conducted. Results The SIRT3 mRNA levels were downregulated in 7 of 8 databases and were related to the diagnosis of AD in 7 databases, with an area under the curve (AUC) of the receiver operating characteristic curve (ROC curve) greater than 50%. Additionally, GO and KEGG analyses showed that SIRT3 downregulation could affect neuroactive ligand-receptor interactions, the MAPK signaling pathway, long-term potentiation, the calcium signaling pathway and axon guidance in AD patients. Conclusions SIRT3 mRNA is downregulated in the brain tissues of AD patients, promoting the progression of AD.