This study examined the antioxidant and anti-inflammatory activities of the water extract of longan pericarp (WLP). The results showed that WLP exhibited radical scavenging, reducing activity and liposome protection activity. In addition, WLP also inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophages. Further, administration of WLP, in the range of 100-400 mg/kg, showed a concentration-dependent inhibition on paw edema development following carrageenan (Carr) treatment in mice. The anti-inflammatory effects of WLP may be related to NO and tumor necrosis factor (TNF-α) suppression and associated with the increase in the activities of antioxidant enzymes, including catalase, superoxide dismutase, and glutathione peroxidase. Overall, the results showed that WLP might serve as a natural antioxidant and inflammatory inhibitor.