Endometrial polyps (EPs) are benign overgrowths of the endometrium, with the potential to cause severe complications, ranging from discomfort to inflammation and infertility. Dysfunction of endometrial fibroblasts may be a critical component leading to the development of polyps. While surgical intervention is the common remedy for severe cases, it comes with drawbacks, including infection, bleeding, and risk of damage to the cervix and adjacent tissues. Adipose-derived mesenchymal stromal cells (ASCs) are at the focus of modern medicine, as key modulators of tissue homeostasis, inflammation and tissue repair, rendering them prime candidate agents for tissue regeneration and cell-based therapies. In the current work, endometrial polyps were isolated from patients admitted to the OB/GYN department at the Galilee Medical Center and extracted fibroblasts (EPFs) were isolated and characterized. ASCs were isolated from healthy patients. The effect of EPF- and ASC-conditioned media (CM) on polyp-derived fibroblasts was evaluated, in both 2D and 3D assays, as well as on the expression of matrix-related gene expression. Herein, EPFs exposed to ASC-CM exhibited reduced migration, invasion, contraction of hydrogels, and extracellular matrix deposition, compared to those exposed to EPF-CM. Altogether, the current work suggests that ASCs may have a modulating effect on fibroblasts involved in forming endometrial polyps and may serve as the basis for conservative treatment strategies aimed at treating severe cases of EPs.