Magnolol (M), a hydroquinone containing an allyl side chain, is one of the major active components ofHoupoea officinalisfor antioxidation and anti-aging. To enhance the antioxidant activity of magnolol, the different sites of magnolol were structurally modified in this experiment, and a total of 12 magnolol derivatives were obtained. Based on the preliminary exploration of the anti-aging effect of magnolol derivatives in aCaenorhabditis elegans(C. elegans) model. Our results indicate that the active groups of magnolol exerting anti-aging effects were allyl groups and hydroxyl on the phenyl. Meanwhile, the anti-aging effect of the novel magnolol derivative M27 was found to be significantly superior to that of magnolol. To investigate the effect of M27 on senescence and the potential mechanism of action, we investigated the effect of M27 on senescence inC. elegans. In this study, we investigated the effect of M27 onC. elegansphysiology by examining body length, body curvature and pharyngeal pumping frequency. The effect of M27 on stress resistance inC. eleganswas explored by acute stress experiments. The mechanism of M27 anti-aging was investigated by measuring ROS content, DAF-16 nuclear translocation, sod-3 expression, and lifespan of transgenic nematodes. Our results indicate that M27 prolonged the lifespan ofC. elegans. Meanwhile, M27 improved the healthy lifespan ofC. elegansby improving pharyngeal pumping ability and reducing lipofuscin accumulation inC. elegans. M27 increased resistance to high temperature and oxidative stress inC. elegansby reducing ROS. M27 induced DAF-16 translocation from cytoplasm to nucleus in transgenic TJ356 nematodes and upregulated the expression of sod-3 (a gene downstream of DAF-16) in CF1553 nematodes. Furthermore, M27 did not extend the lifespan of daf-16, age-1, daf-2, and hsp-16.2 mutants. This work suggests that M27 may ameliorate aging and extend lifespan inC. elegansthrough the IIS pathway.