Abstract Context: Polygonum species have been used in the treatment of several types of inflammatory disorders and cancer. Nevertheless, there are no reports related to the anti-inflammatory and anti-proliferative activities of Polygonum bellardii All. (Polygonaceae). Objective: This study investigated the chemical composition of the methanol extract of P. bellardii. The anti-inflammatory and cytotoxic activities of methanol, n-butanol, ethyl acetate extracts and isolated polyphenols were determined. Materials and methods: The chemical structure of the isolated compounds was elucidated using different spectral techniques. MTT assay was used to evaluate the anti-proliferative activity in HeLa, MCF-7 and HepG-2 cells. Inhibition of 5-lipoxygenase (5-LOX) activity and prostaglandin E2 (PGE2) production in stimulated HepG-2 cells were used to assess the anti-inflammatory activity. Results: The present study resulted in isolation of five compounds (new for the species). They were identified as gallic acid (1), quercetin (2), myricetin (3), quercetin-3-O-β-d-glucopyranoside (5) and myricetin-3-O-α-arabinofuranoside (7). Additionally, a couple of previously isolated compounds such as quercetin-3-O-(5″-acetyl-α-arabinofuranoside) (4) and myricetin-3-O-(5″-acetyl-α-arabinofuranoside) (6) were detected. The n-butanol extract has the highest cytotoxicity in HeLa, MCF-7 and HepG-2 cells, with IC50 values of 15.26, 50.66 and 30.09 µg/ml, respectively. Compound 6 exhibited a marked cytotoxicity in HeLa (IC50 75.04 µg/ml) and HepG-2 (IC50 41.03 µg/ml) cells. Crude extracts and pure compounds inhibited the 5-LOX activity and PGE2 production in a dose-dependent manner (0.1-250 µg/ml). Discussion and conclusion: These results explain the traditional uses of P. bellardii and indicate that polyphenols, despite structural similarity, have different cytotoxic and anti-inflammatory effects.