► Find a new way to improve the antioxidant of whey protein isolate. ► Whey protein isolate (WPI) and seven types of sugars formed MRPs. ► The MRPs exhibited antioxidant activities. ► The MRPs may be used as natural antioxidants in food products. ► Study on the changes of the space and molecular of WPI after Maillard reaction. The objective of this study was to determine antioxidant activities of water-soluble MRPs (Maillard reaction products) from the reactions between whey protein isolate (WPI) and xylose (X), glucose (G), fructose (F), lactose (L), maltose (M) and sucrose (S) at different initial pH values (3, 4, 5, 6, 7, 8 and 9). MRPs derived from the WPI-X system with increasing of pH rendered the highest browning, reducing power and DPPH radical-scavenging activity. SDS–PAGE analyses indicated formation of cross-linked proteins of large molecular mass produced from WPI-X systems. Results of FT-IR analysis indicated that the amide I, II and III bands of WPI from the WPI-X and WPI-G systems were changed by the Maillard reaction. CD spectroscopy showed that β-sheet, β-turns and random coil were increased while the α-helix was decreased after the WPI-G and WPI-X system aqueous solutions were heated. In conclusion, MRPs obtained from the WPI-X system had high antioxidant activity.