Triptolide is a major active compound found in Tripterygium wilfordii., also known as Thunder God Vine. Triptolide has been shown to have anti-inflammatory and anticancer activities. In this study, we examined the effect of dietary supplementation with triptolide on response to environmental stressors and lifespan in vivo using Caenorhabditis elegans as a model system. Treatment with 50 mg/L of triptolide in the growth media increased resistance to oxidative stress and reduced the generation of intracellular reactive oxygen species. We also observed a lifespan-extending activity for triptolide. Both mean and maximum lifespans were significantly increased by supplementation with triptolide. Response to other environmental stressors was modulated by triptolide. The survival after heat shock or UV irradiation was markedly increased in worms treated with triptolide. Unlike many lifespan-extending genetic or nutritional interventions, the longevity phenotype conferred by triptolide did not have the trade-off of a reduction in fertility or a delay in the gravid period. The expressions of hsp-16.2 and sod-3, known to positively correlate with a long lifespan, were significantly upregulated by supplementation with triptolide. These findings suggest that triptolide can exhibit antistress and lifespan-extending effects in vivo, possibly through its antioxidant activity and support the free radical theory of aging, which emphasizes the causative role of oxidative stress in aging.