Polygonum species have strong biological activity due to their important bioactive components. Polygonum species have been studied for enzyme inhibition activity, wound healing, anti-inflammatory, antibacterial, antiviral, antioxidant effects, immunomodulatory activity, anti-aging potential, estrogenic activity and are used abroad as a source of resveratrol. For this purpose, biological activity studies, and phytochemical analysis were carried out in P. aviculare L., P. cognatum Meissn., P. patulum Bieb. subsp. patulum, and P. setosum Jacq. subsp. setosum growing in Turkish flora. Polygonum ethanol extracts were tested for their cholinesterase, elastase, collagenase, and tyrosinase enzyme inhibitory activities with spectrophotometry. P. aviculare root extract had the highest acetylcholinesterase inhibitory activity (IC50= 55.94 ± 2.63 µg/mL), while the best butrylcholinesterase inhibitory activity was observed for P. aviculare (IC50= 17.02 ± 3.42 µg/mL) and P. patulum (IC50= 18.36 ± 0.15). µg/mL) root extracts. All Polygonum root extracts showed moderate inhibitory activity against tyrosinase. In this study indicated that P. aviculare root (IC50= 169.33 ± 3.58 µg/mL) had the highest anti-elastase activity. P. cognatum roots (IC50= 200.30 ± 2.26 µg/mL) have potent inhibition against collagenase. LC-Q-ToF-MS analysis in Polygonum extracts indicated that resveratrol was not present in the extracts.