Sedanolide is a natural compound occurring in edible umbelliferous plants. Celery seed oil, a significant source of sedanolide, Is used as an herbal remedy to treat inflammatory-associated conditions such as gout and rheumatism. The objective of this study was to assess the potential protective properties of sedanolide against hydrogen peroxide (H2O2)- and tert-butyl hydroperoxide (tBOOH)-induced toxicity in HepG2 and CaCo-2 cells. Viability of HepG2 and CaCo-2 cells was unaffected by a 24-h exposure to sedanolide (7-500 muM), however, when the cells were cultured in sedanolide-free medium for a further two cell cycles (72 h), a decrease in cell viability was observed for HepG2 cells previously exposed to 500 muM of the compound. Cells pretreated with sedanolide (100 muM for 24 h) and exposed to either H2O2 or tBOOH did not exhibit statistically significant difference in viability from controls. A significant increase (p < 0.05) in DNA strand breaks, as measured by the comet assay, was observed in HepG2 but not CaCo-2 cells following a 24-h incubation with 500 μM sedanolide. Sedanolide did not modulate H2O2- and tBOOH-induced DNA damage. Sedanolide is relatively nontoxic to cells in culture, however, the protection it afforded against H2O2- and tBOOH-induced toxicity was not statistically significant.