Transcriptomic and bioinformatic analyses were performed to investigate the differentially expressed genes and signaling pathways in the liver related to the role of oleuropein in alleviating type 2 diabetes in db/db mice. The results showed that compared with the db/db control group, 539 genes in the oleuropein treatment group had significant changes, of which 450 genes were significantly up-regulated and 89 genes were down-regulated. The up-regulated and down-regulated differentially expressed genes were annotated in the Gene Ontology database, revealing that they were mainly distributed in cellular processes, cell parts, and binding terms. The results of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the up-regulated differentially expressed genes were mainly enriched in the phosphoinositide 3-kinase-protein kinase-B signaling pathway, which involved a total of 27 differentially expressed genes; the down-regulated differentially expressed genes were mainly enriched in arachidonic acid metabolism and ribosomal biogenesis signaling pathways in eukaryotes, which involved four differentially expressed genes, separately. This study lays the foundation for further elucidating the molecular mechanism by which oleuropein alleviates type 2 diabetes.