Polygonflavanol A (1), a novel flavonostilbene glycoside with an unusual coupling pattern, together with five known stilbene glycosides (2–6), was isolated from the roots of Polygonum multiflorum. The structures were elucidated on the basis of extensive spectroscopic analysis and chemical evidence. The absolute configuration of 1 was further determined by CD analysis. Most of the compounds could inhibit nitric oxide (NO) secretion of RAW264.7 cells in respond to lipopolysaccharide (LPS) in a dose dependent manner. Among them, compound 2 displayed the highest inhibitory activity.