Argentatins A and B are triterpenes isolated from Parthenium argentatum (guayule), a shrub primarily known for producing hypoallergenic natural rubber. Beyond this use, its resin fraction contains secondary metabolites with bioactive potential. This study evaluated the effects of argentatins A and B on cancer cell invasion and angiogenic structure formation using preclinical models. Transwell assays were performed on colon and lung cancer cell lines, including chemotherapy-resistant models, and antiangiogenic activity was assessed in HMEC-1 endothelial cells. Results showed that both compounds significantly reduced cell invasion (particularly in colon cancer) and strongly inhibited capillary-like structure formation, indicating robust antiangiogenic effects. Interestingly, an opposite response was observed in cisplatin-resistant cells, suggesting differential sensitivity. These findings support the potential of argentatins as bioactive agents targeting key processes such as tumor invasion and angiogenesis, opening new perspectives for their future oncological applications.