The aim of this study was to investigate the utilization of 6-gingerol at different levels (50 and 100 mg/kg) as natural antioxidants for retarding lipid oxidation in red drum fillets during refrigerated storage. The results showed that 6-gingerol had a high scavenging capacity of 2, 2-diphenyl-1-picryl hydrazyl (DPPH) and 2, 2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals in vitro. With addition of 6-gingerol, especially when the higher level (100 mg/kg) was used, lipid oxidation and hydrolysis in red drum fillets was significantly retarded indicating by the low peroxide value (PV), thiobarbituric acid reactive substances (TBARS), conjugated diene (CD), free fatty acid (FFA), hexanal content. Moreover, the results of colour and sensory evaluation confirmed the feasibility of 6-gingerol by maintaining the edible quality of red drum during refrigerated storage. Taken together, 6-gingerol could be applied as natural antioxidants to minimize lipid oxidation and to extend shelf life of fish fillets.