| Summary: | <i>Polygonum hydropiper</i> L. is a traditionally used medicinal plant. The present study was designed to explore the α-amylase inhibitory, antioxidant, and antimicrobial activities of <i>Polygonum hydropiper</i> L. Polarity-based solvent extracts (<i>n</i>-hexane, acetone, chloroform, methanol, ethanol, and water) of <i>Polygonum hydropiper</i> leaves and stem were used. Antioxidant activity was assessed by free radical scavenging assay (FRAP) and 2,2-diphenylpicrylhydrazyl (DPPH) free radical scavenging activity methods. Quantitative phytochemical analyses suggested that the stem of <i>Polygonum hydropiper</i> L. contains higher levels of bioactive compounds than its leaves (<i>p</i> < 0.05). The results suggested that stem-derived extracts of <i>Polygonum hydropiper</i> L. are more active against bacterial species, including two Gram-positive and three Gram-negative strains. Moreover, our results showed that the bioactive compounds of <i>Polygonum hydropiper</i> L. significantly inhibit α-amylase activity. Finally, we reported the polarity-based solvent extracts of <i>Polygonum hydropiper</i> L. and revealed that the stem, rather than leaves, has a high antioxidant potential as measured by FRAP and DPPH assay with IC<sub>50</sub> values of 1.38 and 1.59 mg/mL, respectively. It may also be deducted from the data that the <i>Polygonum hydropiper</i> L. could be a significant candidate, which should be subjected to further isolation and characterization, to be used as an antidiabetic, antimicrobial and antioxidant resource in many industries, like food, pharmaceuticals and cosmetics.
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