Resveratrol and quercetin are polyphenols abundant in frequently consumed fruits, vegetables, and red wine. They have many biological activities, including antitumor, anti-inflammation, and antioxidation effects. This study evaluates the chemopreventive potential of resveratrol and quercetin against pancreatic cancer and investigates some of the underlying mechanisms. We report that resveratrol and quercetin suppress pancreatic tumor growth and that resveratrol extends life expectancy in a tumor bearing mouse model. Further, these two polyphenols inhibit growth of pancreatic cancer cell line, Panc02, in vitro. Results suggest that mechanisms may include induction of expression of caspase 3/8, causing DNA fragmentation, and arresting cells in G1 phase of the cell cycle. Cell invasion data reveals that both resveratrol and quercetin are able to decrease tumor cell invasion through an endothelial barrier. These data suggest that resveratrol and quercetin may be beneficial in pancreatic cancer treatment and metastasis prevention.