Persicaria strigosa (R.Br.) Nakai. (Family Polygonaceae) is an important plant of Assam, having several ethnobotanical uses. Tribal communities consume leaf extracts to cure helminth infection. The present study investigated the antioxidant, phytochemicals, and anthelmintic activity of P. strigosa. Total phenolic and flavonoid contents were estimated following standard methods. Antioxidant properties were analyzed by TAC, FRAP, DPPH, ABTS, and TBARS assays. Anthelmintic activity of plant was investigated in Paramphistomum sp. treated with 5 mg/mL, and paralysis and death times were recorded. The most potent solvent extract was performed GC–MS analysis to identify the phytocompounds. Plant extract-treated parasites were further analyzed for biochemical changes. Additionally, molecular docking was performed to study the binding affinities between phytocompounds and enzymes. P. strigosa showed rich phenolics, flavonoids, and antioxidant properties. Ethyl acetate and methanolic extracts showed more powerful antioxidant properties than other extracts. In vitro anthelmintic study found ethyl acetate and diethyl ether the most active extracts. Treated parasites showed a significant decrease in enzyme activity. The highest inhibition was observed in AchE, followed by MDH, LDH, ALP, and ACP. GC–MS study identified 12 probable compounds from the ethyl acetate extract of P. strigosa. Molecular docking showed the strongest binding affinity between the phytocompounds and AchE enzyme (− 7.6 kcal/mol). Overall, compounds C6, C7, and C12 showed better binding affinity compared to other compounds. The in vitro helminth bioassays and biochemical analysis suggest Persicaria strigosa a possible anthelmintic agent. However, isolation and characterization of bioactive compound(s) may promise new drug candidates for helminth infections.