The　anticancer　properties　of　ursolic　acid　(UA)　and　metformin　(Met)　have　been　well　demonstrated.　However,　whether　these　compounds　can　act　synergistically　to　prevent　and　treat　cancer　is　not　known.　We　present　in　this　study,　the　synergism　between　UA　and　Met,　and　that　of　a　new　codrug　made　of　UA　and　Met　(UA-Met)　against　several　cancer　cell　lines.　The　combination　of　high　concentration　of　UA　(25,　50,　75,　100　μM)　and　Met　(5,　10,　20,　40　mM)　resulted　in　synergetic　cytotoxicity　on　MDA-MB-231　and　MCF-7　cells　(CI　＜　0.8).　Molecular　and　cellular　studies　showed　that　codrug　UA-Met　significantly　inhibited　the　invasion　(~55.3　±　2.74%)　and　migration　(~52.4　±　1.57%)　of　TGF-β　induced　breast　cancer　MDA-MB-231　and　MCF-7　cells　in　vitro　at　low　concentration　of　10　μM.　These　effects　were　accompanied　by　down-regulation　of　CXCR4,　uPA,　vimentin,　E-cadherin,　N-cadherin,　and　MMP-2/9　proteins　expression　and　regulation　of　the　AMPK/m-TOR　signaling　pathways　as　expected　from　UA　and　Met.　Moreover,　UA-Met　could　reduce　the　progression　of　pulmonary　metastasis　by　4T1　cells　(63.4　±　3.52%)　without　influencing　the　glucose　blood　level　in　mice.　Our　study　suggests　that　the　codrug　UA-Met　is　safe　and　effective　in　preventing　cancer　metastasis　and　possibly　treatment　of　cancer.　©　2017　American　Chemical　Society.