ABSTRACT Urolithiasis plagues are common urinary disease in worldwide. Siddha medicine is one of the traditional systems of medicines practiced in the southern India. Amurthathi Chooranam is a classical Siddha Poly herbal formulation which was analyzed by molecular docking for Urolithiasis. The present study is aimed to accomplish the In Silico computational binding of phytocomponents of Amurthathi Chooranam with the core amino acids (CYS 527, PRO 528, HIS 529, GLY 534, ARG 583, THR 585, ARG 586) of the target protein Tamm–Horsfall protein (PDB) - 4WRN which is involved in calcium oxalate crystallization for management of urolithiasis. Docking calculations were carried out for retrieved phytocomponents against target protein Tamm–Horsfall protein. Essential hydrogen atoms, Kollman united atom type charges, and solvation parameters were added with the aid of AutoDock tools. Docking simulations were performed using the Lamarckian genetic algorithm (LGA) and the Solis & Wets local search method. Initial position, orientation and torsions of the ligand molecules were set randomly.Total 9 bioactive lead compounds were retrieved from the herbs present in Amurthathi Chooranam such as Alpha-phellandrene, Elemene, Elemicin, Tinosporide, Nerolidol, Eugenol, Quercetin, Syringic Acid and Morphine possess maximum of 3-4 interactions with the core active amino acid residues present on the target protein Tamm–Horsfall protein. Based on the results it was concluded that the above mentioned compounds exerts anti-urolithiasis activity by preventing calcium oxalate crystallization which inhibit the target Tamm–Horsfall protein for management of urolithiasis. Keywords: Molecular Docking, Amurthathi Chooranam, Antiurolithiatic activity, Tamm–Horsfall protein