Metformin is one of the first-line and widely-used drugs in patients with T2DM due to its safety profile, clinical efficacy and cheap cost. It is clearly that metformin has benefits on lowering hyperglycemia and diabetes-related complications in clinical use. The classic effect of metformin is to reduce hepatic glucose production by inhibiting gluconeogenesis in liver and increase glucose utilization in peripheral tissues. Metformin targets mitochondrial respiratory chain complex I to specifically reduce reactive oxygen species generation to protect cells against oxidative stress-induced cell apoptosis. AMPK complex is a key factor in the action of metformin; however it is inconclusive that whether metformin activate AMPK directly or indirectly. In addition, more and more studies showed that metformin act on gut microbiota to exert anti-hyperglycemia effect. Emerging evidence showed that metformin has off-label function on antitumor therapy; however the underlying mechanism of this property of metformin still remains elusive. Taken together, in this review we provide a new perspective on metformin and repurpose its novel and promising application in antitumor therapy.