Esculetin is a coumarin lactone found in chicory and other plants; it exhibits anticoagulant, anti-obesity, anti-hyperlipidemic, anti-inflammatory, anticancer, antioxidative, and neuroprotective activities. Esculetin decreases levels of NO, PPARγ, TNF-α, and MCP-1 and increases levels of heme oxygenase 1 (HO-1) in macrophages. In animal models of Parkinson’s disease, esculetin inhibits MPTP-induced neurotoxicity and neuronal apoptosis. In high fat diet-fed rats, this compound decreases body weight, triglyceride levels, total cholesterol, and glucose levels. Additionally, esculetin induces cell cycle arrest, DNA fragmentation, activation of caspases 3 and 9, reduction of the mitochondrial membrane potential, and apoptosis in acute promyelocytic leukemia (APL) cells. Esculetin also inhibits proliferation of colon cancer cells by directly inhibiting β-catenin. This compound also acts as a radical scavenger in vitro.