The changes of physical stability and protein-lipid co-oxidation of oil-in-water (O/W) emulsions which stabilized by whey protein isolates (WPI) and ethanol pre-treated WPI (EWPI) under different homogenization methods were investigated. Compared with WPI, EWPI could obviously enhance the O/W emulsion's stability due to smaller particle size and higher level of adsorbed proteins. Moreover, protein-lipid co-oxidation was observed in both WPI and EWPI stabilized O/W emulsions and controlled by the characteristics of the adsorbed proteins. EWPI protect themselves from attacked of lipid oxidation products more effectively than WPI, showing lower N'-formyl-L-kynurenine or carbonyl contents and degree of aggregation, as well as higher fluorescence intensity. Furthermore, high-pressure homogenization induced higher levels of adsorbed proteins in O/W emulsions than ultrasound homogenization, resulting in a higher degree of protein oxidation and lower degree of lipid oxidation. Therefore, EWPI can be applied as an efficient emulsifier in emulsion foods with higher physical and oxidative stabilities.