Siraitia grosvenorii pomace (SGP) was processed by solid-state fermentation with Eurotium cristatum. Metabolite differences between non-fermented Siraitia grosvenorii pomace (NFSGP) and E. cristatum fermented Siraitia grosvenorii pomace (FSGP) were investigated by LC-MS/MS-based untargeted metabolomic analysis. The antioxidant and anti-aging effect of NFSGP and FSGP was investigated through in vitro and in vivo assays using Caenorhabditis elegans model. Results showed that 263 metabolites had significant changes after fermentation. Fermentation with E. cristatum significantly increase most polyphenols, flavonoids and alkaloids, such as sinapic acid, quercetin and indole. The antioxidant activities of SGP were also significantly enhanced after fermentation by E. cristatum. Furthermore, NFSGP and FSGP could significantly prolong the life-span and enhanced the oxidative and heat stress resistance of C. elegans, and FSGP exhibited greater effects. Our study revealed that fermentation with E. cristatum could improve the nutritional value of SGP. © 2023 Elsevier Ltd