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Wild edible mushrooms are one of the most fascinating nutraceuticals because of their pleasant texture, peculiar aroma, and tremendous therapeutic potential; they have been used since ancient times. In this study we evaluated the antioxidant potential of 4 wild edible mushrooms-Cantharellus tropicalis, C. cibarius, Lentinus edodes, and Russula delica-collected from Mizoram, India. We performed in vitro and in vivo studies using a Saccharomyces cerevisiae stress response mechanism as the model system. Among the 4 mushrooms, C. cibarius exhibited the most significant antioxidant activity both in vitro and in vivo, followed by L. edodes, R. delica, and C. tropicalis. Gas chromatography-mass spectrometry analysis of methanolic extracts of the mushrooms revealed the presence of substantial amounts of fatty acids, fatty acid esters, and other bioactive constituents. The in vitro antioxidant activity was corroborated by in vivo studies using an S. cerevisiae oxidative stress response mechanism. In spot assays, the C. cibarius methanolic extract showed the highest scavenging potential in wild and mutant (sodlΔ and tsalΔ) strains of S. cerevisiae. These results were confirmed further by determining the level of reactive oxygen species through the use of fluorescent microscopy and intensity studies. The results suggested the efficacy of wild edible mushrooms as prominent therapeutic agents and that they have tremendous nutraceutical properties.