We investigated the anti-aging effects of Ludwigia octovalvis (Jacq.) P. H. Raven (Onagraceae), an extract of which is widely consumed as a healthful drink in a number of countries. Using the fruit fly, Drosophila melanogaster, as a model organism, we demonstrated that L. octovalvis extract (LOE) significantly extended fly lifespan on a high, but not a low, calorie diet, indicating that LOE may regulate lifespan through a dietary restriction (DR)-related pathway. LOE also attenuated age-related cognitive decline in both flies and in the senescence-accelerated-prone 8 (SAMP8) mouse, without causing any discernable negative trade-offs, including water intake, food intake, fecundity, or spontaneous motor activity. LOE contained high levels of polyphenols and flavonoids, which possess strong DPPH radical scavenging activity, and was shown to attenuate paraquat-induced oxidative damage and lethality in flies. Gas chromatography-mass spectrometry (GC-MS) analyses identified 17 known molecules, of which β-sitosterol and squalene were the two most abundant. We further demonstrated that β-sitosterol was capable of extending lifespan, likely through activating AMP-activated protein kinase (AMPK) in the fat body of adult flies. Taken together, our data suggest that LOE is a potent anti-aging intervention with potential for treating age-related disorders.