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ETHNOPHARMACOLOGICAL RELEVANCE Medicinal herb Cichorium intybus L. (chicory) has been used traditionally for the treatment of various diseases, including diabetes. One of the promising therapeutic options to treat diabetes is replacing the degenerative pancreatic β cells by stem cell-derived IPCs (insulin-producing cells). AIM OF THE STUDY By the combination of cell therapy as a modern approach and traditional medicine, the current study was designed to evaluate the effects of chicory leaf extract (LE) on the differentiation potential of P19 EC cells (an embryonal carcinoma stem cell line) into IPCs. MATERIALS AND METHODS The plant (voucher no. 4567) were collected and deposited in the herbarium of Shahrekord University. In vitro experiments were designed to compare the effects of various concentrations of LE on the differentiation potential of P19 EC cells. RESULTS The differentiated cells showed morphological characteristics of pancreatic β cells. They could also synthesized and secreted insulin when exposed to glucose. Moreover, the cells expressed specific proteins and genes of mature pancreatic β cells. CONCLUSIONS In conclusion, LE as a natural herbal extract was efficiently able to induce the differentiation of P19 EC cells into the clusters similar to pancreatic islets with the molecular, cellular and functional characteristics of mature β cells.