Anthelmintic resistance remains a significant challenge for the treatment of gastrointestinal parasites. The search for novel compounds is costly, but the traditional knowledge of Sashechalam hill practitioners led us to investigate Grewia bilamellata Gagnep. We assessed its anthelmintic activity against Indian earthworms (Pheretima posthuma) using various extract concentrations (10, 20, 50, and 100 mg/mL), with albendazole as the positive control and normal saline as the negative control. The duration of paralysis and death indicated anthelmintic efficacy. G. bilamellata ethanol extract (GBEE) demonstrated a significant concentration-dependent effect. The IC50 values for albendazole, G. bilamellata petroleum ether extract (GBPE), G. bilamellata ethyl acetate extract (GBEA), and GBEE were 181.947, 310.337, 270.488, and 223.468 mg/mL, respectively. GBEE exhibited potent anthelmintic activity comparable to that of albendazole, with the lowest paralysis and death rates in the model. The HR-LC-MS analysis of GBEE identified 38 phytoconstituents, of which 22 compounds obeyed Lipinski’s rule. Molecular docking with β-tubulin revealed that 15 compounds exhibited superior binding energy (-8.3 to -6.3 kcal/mol) compared to albendazole (-6.1 kcal/mol). Further investigations are crucial to isolate and evaluate these compounds for the development of new anthelmintic drugs. Our findings support the traditional use of G. bilamellata Gagnep. as an anthelmintic, and highlight its potential for future therapeutic applications. پرونده مقاله