Graves' disease (GD), an autoimmune disorder, scars majority of women worldwide, causing hyperthyroidism, Graves's ophthalmopathy and goitre. Thyroid Peroxidase (TPO) is an active target of anti-thyroid drugs, Methimazole and Propylthiouracil, which inhibit the enzyme function of catalysing the thyroid hormones synthesis. Most of the protein-drug interaction studies so far have been focussed mainly at in vivo level, or by using Myeloperoxidase and Lactose peroxidases as TPO surrogates for the same. This makes the molecular interaction of TPO with the drugs crucial to understand. In this study, we used the molecular dynamics (MD) to study the molecular interaction differences between TPO 201-500 and both drugs. The binding free energy calculation done using Molecular Mechanics Poisson-Boltzmann (MM-PBSA) and generalized Born and surface area continuum solvation (GBSA) results indicated that both drugs bind strongly to TPO 201-500 , with Propylthiouracil having slightly higher binding energy than Methimazole. We found that both drugs interacted with the residues-Asp238, His239, Phe243, Thr487 and His494 through hydrophobic interactions and formed stable hydrogen bonds with residue Arg491 of TPO 201-500 . Since both drugs engage residues-Asp238, His239 and His494 which falls within the proximal heme binding site and catalytic site of TPO 201-500 , we can conclude that these drugs may be conducive in inhibiting the enzymatic activity of TPO 201-500 .