This study presents the first comprehensive evidence of Telfairia occidentalis exhibiting potent antifibrotic activity in MSG-induced uterine leiomyoma models and synergistic interactions between beta-carotene and lutein, phytoconstituents of Telfairia occidentalis, with STEAP4, a fibroid-associated enzyme, highlighting a novel mechanism of action. Here, STEAP4 is linked to uterine corpus leiomyoma.