Objective To study the chemical constituents from Desmodium triquetrum and their antihyperlipidemic activities. Methods The constituents of D. triquetrumwere isolated and purified using various column chromatographies. Their chemical structures were elucidated using extensive spectroscopic methods. The lipid-lowering effects of the isolates were evaluated in HepG2 cells. Results Nine compounds were obtained from the ethanol extract of D. triquetrum and determined to be 6'-O-cis-p-coumaroyl- 3,5-dihydroxyphenyl-β-D-glucopyranoside (1), tadehaginoside (2), rutin (3), quercetin-3-O-β-D-glucopyranoside (4), quercetin-3-O-β-D-galactopyranoside (5), 6-O-(E)-p-hydroxy-cinnamoyl-β-glucose (6), 6-O-(E)-p-hydroxy-cinnamoyl-α-glucose (7), kaempferol-3-O-β-D-rutinoside (8), and 3-O-β-D-galacopyranosyl (6-1)-α-L- rhamnosyl quercetin (9). Compounds 1 and 2 significantly reduced the intracellular content of total cholesterols and triglycerides. Conclusion Compound 1 is a new phenolic compound and exhibits potent anti-hyperlipidemic activity. Additionally, compounds 6 and 7 are isolated from D. triquetrum for the first time.