Desmoplastic tumors have an abundance of stromal cells and the extracellular matrix which usually result in therapeutic resistance.Current treatment prescriptions for desmoplastic tumors are usu-ally not sufficient to eliminate the malignancy.Recently,through modulating cancer-associated fibro-blasts(CAFs)which are the most abundant cell type among all stromal cells,natural products have improved chemotherapies and the delivery of nanomedicines to the tumor cells,showing promising abil-ity to improve treatment effects on desmoplastic tumors.In this review,we discussed the latest advances in inhibiting desmoplastic tumors by modeling CAFs using natural products,highlighting the potential therapeutic abilities of natural products in targeting CAFs for cancer treatment.