Seaweeds are rich sources of bioactive compounds with potential health benefits. Anti-stress effects of the cultivated red alga, Chondrus crispus, were investigated in the Caenorhabditis elegans model. Methanolic extracts of C. crispus (CCME) enhanced C. elegans tolerance to juglone-induced oxidative stress and increased life span; however water extracts did not show such effects. CCME treatment reduced reactive oxygen species (ROS) in the worms and increased the transcription of stress response genes; sod3, hsp16.2, daf16 and skn1. The chemical profile of CCME revealed the presence of unsaturated fatty acids, pigments, galactolipids, floridoside, isothionic acid, taurine, phenylalanine and l-citruline. Bioassay guided fractionation revealed that fatty acids, lipids and pigments imparted stress tolerance. Taken together, our results suggest that organic fractions of cultivated C. crispus impart oxidative stress tolerance in C. elegans, possibly by altering the stress response pathways.