Purpose <p>This study aimed to determine the various activities and chemical contents of endemic <i>Polygonum samsunicum</i> L. (Samsun madımağı) extracts prepared using different polarity solvents, spectrophotometrically.</p> Methods <p>The phytochemical analysis, phenolic and flavonoid contents of <i>P. samsunicum</i> extracts were determined spectrophotometrically. The extracts' antioxidant, DNA protection, antibacterial, antiproliferative, and enzyme inhibitory activities were tested and evaluated using standards.</p> Results <p>The total phenolic and flavonoid contents were highest in ethanol, water, and methanol extracts. The major ingredients of the extracts were catechin, quercetin-3-β-D-glucoside, and fumaric acid. The methanol extract was determined to have higher H₂O₂ scavenging activity (26.94±4.04 µg/mL). The water extract showed lipid peroxidation inhibition (12.51±4.22 µg/mL), deoxyribose protection (41.48±2.44 µg/mL), and O₂·⁻ scavenging activity (15.43±2.92 µg/mL). The water, methanol, and ethanol extracts exhibited inhibitory effects against esterase enzymes related to Alzheimer’s disease. The ethanol extract showed promising DNA protection potential and inhibited the proliferation of the HeLa cancer cell line. The antibacterial activities of ethanol, methanol, water, and acetone extracts were the most effective against bacteria. The interactions of the major components with p53, BRAF, and BCL2 proteins in HeLa cancer cell lines were evaluated using molecular docking. Here, all three components displayed high interaction with the BRAF protein and were recorded to be stable in molecular dynamics (MD) simulations. The binding energies of the interaction of these three compounds with the BRAF protein were determined by MM/PBSA analysis.</p> Conclusion <p>Overall, the composition and activity findings of <i>P. samsunicum</i> extracts have shown valuable and effective food potential for human health.</p>