Although whey protein isolate (WPI) has multiple functionalities, oxidation of WPI affects its application in the food industry. However, extrusion potentially inhibits oxidation of WPI. In this work, impacts of extrusion on physicochemical, functional and intro digestive properties of WPI oxidated by malondialdehyde (MDA) were investigated. MDA-induced consumption of free SH-group and amino group, and generation of carbonyl group in extruded WPI (EWPI) were lower than those of WPI, which decreased with extrusion temperature ranged from 50 to 100 °C. High resolution microscopical observation showed a peripheral irregular fragmented structure of MDA-oxidated WPI, and some aggregates of MDA-oxidated EWPI. At low extrusion temperature (50 °C), hydrophobicity, zeta-potential, emulsifying activity, foaming ability and digestibility of MDA-oxidated EWPI were increased by 16.65, 32.94, 62.95, 196.09 and 21.38%, respectively, compared with MDA-oxidated WPI. Thus, this research could provide an effective approach for reducing MDA-induced oxidation of food proteins during the food processing and storage.