Recent experimental studies have shown that the FePt nanoparticles (NPs) assembled on graphene exhibit enhanced durability and catalytic activity for oxygen reduction reaction (ORR) than Pt-only catalysts. In this work, we have performed density functional theory calculations to investigate the stability and reactivity of several FePt NPs deposited on defective graphene for ORR, where n is adopted as 0, 1, 2, and 3, respectively. The results indicate that the alloying between Fe and Pt can enhance the stability of NPs and promote their oxygen reduction activity. Moreover, the monovacancy site in the graphene can provide anchoring sites for these bimetallic NPs by forming strong metal-substrate interaction, ensuring their high stability. Importantly, the O adsorption on these composites is weakened in various ways, which is ascribed to the change in their averaged d-band center. Thus, these composites exhibit superior catalytic performance in ORR by providing a balance in the O binding strength that allows for enhanced turnover. Our results may be useful to unravel the high stability and reactivity of defective graphene-FePt NPs for ORR from a theoretical perspective. [ABSTRACT FROM AUTHOR]