Increased oceanic temperature due to climatic change is gradually decreasing the production rates of Pyropia yezoensis in South Korea, which accounts for 50 % of the global supply. This study demonstrates the antioxidant property of a newly developed edible marine red algae, heat-resistant P. yezoensis (HrP). The water extract of HrP displayed a notably higher reactive oxygen species (ROS) scavenging effect on DPPH, alkyl, hydroxyl radicals, and H2O2 than the commercial P. yezoensis water extract. To increase the radical scavenging ability of HrP, it was enzymatically hydrolyzed using seven enzymes (Alcalase, Celluclast, Flavourzyme, Neutrase, Protamex, Ultraflo, and Viscozyme). These enzymes-assisted HrP hydrolysates (EHrPs) were evaluated for their free radical scavenging activity. Among them, Neutrase-assisted HrP hydrolysate (NHrP), containing the highest protein content, showed a significant protective effect against H2O2-induced cytotoxicity in Vero cells. The 10 kDa molecular weight cut-off fractionation of NHrP revealed that the filtered fraction (10B; ≤10 kDa) was superior to the unfiltered fraction (10A; >10 kDa) in antioxidant activity. The characterization of the three fractions indicated that the high radical scavenging function mainly depends on the level of proteins. Moreover, 10B treatment ameliorated H2O2-induced oxidative stress in Vero cells and zebrafish embryos (increased survival percentage, and decreased cell death and ROS formation). These data suggest that HrP might be a potential antioxidant for nutraceutical industries.