In the screening search for NF-κB inhibitory and PPAR transactivational agents from medicinal plants, a methanol extract of the whole plant of Tacca plantaginea and its aqueous fraction showed the significant activities. Bioassay-guided fractionation combined with repeated chromatographic separation of the aqueous fraction of the methanol extract of T. plantaginea resulted in the isolation of two new diarylheptanoid glycosides, plantagineosides A (1) and B (2), an unusual new cyclic diarylheptanoid glycoside, plantagineoside C (3), and three known compounds (4-6). Their structures were determined by extensive spectroscopic and chemical methods. Compounds 3-6 significantly inhibited TNFα-induced NF-κB transcriptional activity in HepG2 cells in a dose-dependent manner, with IC(50) values ranging from 0.9 to 9.4 μM. Compounds 1-6 significantly activated the transcriptional activity of PPARs in a dose-dependent manner, with EC(50) values ranging from 0.30 to 10.4 μM. In addition, the transactivational effects of compounds 1-6 were evaluated on three individual PPAR subtypes, including PPARα, γ, and β(δ). Compounds 1-6 significantly enhanced the transcriptional activity of PPARβ(δ), with EC(50) values in a range of 11.0-30.1 μM. These data provide the rationale for using T. plantaginea and its components for the prevention and treatment of inflammatory and metabolic diseases.