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Antioxidants are often investigated as a promising strategy for extending lifespan. Accordingly, there is significant interest in novel antioxidant compounds derived from natural sources such as plant extracts. However, because lifespan studies are laborious and expensive to conduct, candidate compounds are frequently selected based simply on their in vitro antioxidant efficacy, with the implicit assumption that in vitro antioxidants are also in vivo antioxidants, and that in vivo antioxidants will decrease functionally relevant oxidative damage and thereby extend lifespan. We investigated the validity of these assumptions in the model organism, Caenorhabditis elegans. Nematodes were exposed to 6 plant extracts, selected out of a total of 34 based on a simple in vitro antioxidant assay. We found no correlation between in vitro and in vivo antioxidant capacities. Antioxidant efficacies were also not predictive of lifespan benefits. Further studies into those extracts that produced significant lifespan extension indicated that a direct antioxidant effect is unlikely to be the main factor responsible for the modulation of nematode lifespan.