Background: The relationship between cancer and type 2 diabetes is well documented. However, studies are very limited to test new therapies for both diseases in the same biological system. This study was conducted to test the potential of two antidiabetic plants from Jordan (Varthemia iphionoides and Pelargonium graveolens) to treat breast cancer implanted in diabetic mice. Materials and Methods: Different solvent extracts of both plants were prepared, and the in vitro antiproliferative activity was tested against MCF-7, T47D, and EMT6/P breast cancer cell lines in addition to Vero normal cell lines. Normal as well as diabetic Balb/C mice were transplanted with EMT6/P cell line, and in vivo antitumor activity was assessed for the most potent plant extract according to the in vitro results. Histological examination of tumors was performed using standard hematoxylin and eosin staining protocol. Apoptosis was detected using TUNEL colorimetric assay. Vascular endothelial growth factor expression of cancer cells was detected using ELISA. Aspartate aminotransferase, alanine aminotransferase, and creatinine were measured as well as interferon-gamma, interleukin-2 (IL-2), IL-4, and IL-10. Results: V. Iphionoides dichloromethane (DCM) extract was the most potent extract and could inhibit cell growth of breast cancer cell lines (EMT6, MCF-7, and T47D). It showed high ability in targeting growth and progression of breast cancer inoculated in diabetic and non-diabetic mice. Conclusion: V. iphionoids DCM extract is a promising therapeutic option to treat breast cancer in diabetic cases. However, further studies are essential to characterize the active ingredients in this extract.