Medicinal plants are important sources of potentially therapeutic biochemical drugs. Crocus sativus L. has been used to treat various diseases in China, the Republic of Korea and Japan. The present study investigated the protective effect of C. sativus L. extract in Drosophila melanogaster intestinal immunity. Wild‑type flies were fed standard cornmeal‑yeast medium and used as controls, and flies supplemented with 1% C. sativus L. aqueous extract in standard medium were used as the experimental group. Following the ingestion of the various toxic compounds, the survival rate of the flies was determined. Cell viability and levels of reactive oxygen species (ROS) were detected using 7‑amino‑actinomycin D and dihydroethidium staining, respectively. The present study demonstrated that aqueous extracts of C. sativus L. may significantly increase the lifespan and survival rate of adult flies. Additionally, C. sativus L. may decrease epithelial cell death and ROS levels, resulting in improved intestinal morphology. These findings indicated that C. sativus L. had a protective effect against intestinal injury and may extend the lifespan of Drosophila. Therefore, the findings of the present study may improve the understanding of clinical researchers on the complex effects of C. sativus L. in intestinal disorders.