Heatstroke (HS) presents a major health threat, especially during summer, and is linked to myocardial injury and persistent cardiovascular complications.Curcumin has shown promise in treating myocardial damage, but its mechanisms in HS-induced myocardial damage remain unclear. We integrated curcumin targets from BATMAN-TCM, DGIdb, and PharmMapper, and identified HS-related targets from GeneCards and OMIM. The intersection of these targets was identified using Venn diagrams, and subsequently analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis.Protein interactions were analyzed using STRING and visualized in Cytoscape to screen core proteins. Molecular docking was performed with these proteins and curcumin. HS mouse model was constructed for pathological assessments and WB validation of core protein expression. We identified 132 potential therapeutic targets and selected AKT1, Bad, and CASP3 as our targets for validation. Molecular docking indicated that these proteins all have good affinity with curcumin. In HS mouse model, we observed that HS led to significant myocardial cell edema, disordered arrangement, and pronounced mitochondrial swelling accompanied by the destruction of cristae. The application of curcumin effectively alleviated myocardial cell edema and the degree of mitochondrial swelling. WB revealed that HS decreased p-Akt and p-Bad while increasing cleaved-caspase-3. Curcumin treatment reversed these effects, inhibiting HS-induced myocardial cell apoptosis. Our research demonstrates that curcumin effectively safeguards against HS-induced myocardial injury in mice, potentially through the modulation of the Akt/Bad/caspase-3 pathway.