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Although the rhizomes of Rheum nobile Hook. f. et Thoms (Polygonaceae) are widely used in Tibetan medicine, no previous investigations regarding the biological activities and rarely chemical constituents of this plant have been reported. As part of an ongoing search for novel bioactive agents, a phytochemical investigation of R. nobile led to the isolation of two new compounds Rheumone B (1) and piceatannol-4'-O-β-D-(6″-O-acetyl)-glucoside (2), together with 15 known compounds by gel filtration over Sephadex LH-20 and preparative HPLC. Their structures were determined by combined spectroscopic methods. Compounds 1-10 were evaluated for their ability to scavenge 2,2-diphenyl-1-picrylhydzyl (DPPH) radical and compounds 7-10 showed relatively strong scavenging abilities with IC50 values from 2.76 μM to 11.80 μM. In conclusion, naphthalene glycosides, stilbene glycosides, flavanols, especially anthraquinones are main chemical constituents of this plant. The ability to scavenge DPPH radical of compound 8 was the highest among compounds 1-10.