Ischemic strokes (ISs) are commonly treated by intravenous thrombolysis using a recombinant tissue plasminogen activator; however, successful treatment can only occur within 3 hours after the stroke. Therefore, it is crucial to determine the causes and underlying molecular mechanisms, identify molecular biomarkers for early diagnosis, and develop precise preventive treatments for strokes. We aimed to clarify the differences in gene expression, molecular mechanisms, and drug prediction approaches between IS and myocardial infarction (MI) using comprehensive bioinformatics analysis. The pathogenesis of these diseases was explored to provide directions for future clinical research. The IS (GSE58294 and GSE16561) and MI (GSE60993 and GSE141512) datasets were downloaded from the Gene Expression Omnibus database. IS and MI transcriptome data were analyzed using bioinformatics methods, and the differentially expressed genes (DEGs) were screened. A protein–protein interaction network was constructed using the STRING database and visualized using Cytoscape, and the candidate genes with high confidence scores were identified using Degree, MCC, EPC, and DMNC in the cytoHubba plug-in. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs were performed using the database annotation, visualization, and integrated discovery database. Network Analyst 3.0 was used to construct transcription factor (TF) – gene and microRNA (miRNA) – gene regulatory networks of the identified candidate genes. The DrugBank 5.0 database was used to identify gene–drug interactions. After bioinformatics analysis of IS and MI microarray data, 115 and 44 DEGS were obtained in IS and MI, respectively. Moreover, 8 hub genes, 2 miRNAs, and 3 TFs for IS and 8 hub genes, 13 miRNAs, and 2 TFs for MI were screened. The molecular pathology between IS and MI presented differences in terms of GO and KEGG enrichment pathways, TFs, miRNAs, and drugs. These findings provide possible directions for the diagnosis of IS and MI in the future.