Protozoan are parasitic organisms that can cause significant diseases worldwide, such as Chagas disease, African sleeping sickness, and Leishmaniasis. In this study, we performed docking studies on type II tryparedoxin-dependent peroxidase (PDB ID: 2VUP) using a Zinc database having natural products library and FDA-approved drugs. The top compounds identified are F1762-0560, F1855-0030, FDA_339, FDA_461, tetrahydrobenzo-tetraphenoxirene, and ketoconazole. These compounds were further performed the molecular dynamics simulations studies. The docking results has suggested that top Docking Scores compounds are F17620560 (-8.6 kcal/mol), F1855-0030(-7.8 kcal/mol), FDA_339 (-7.0 kcal/mol), FDA_461 (-7.0 kcal/mol), tetrahydrobenzo-tetraphenoxirene (-7.5 kcal/mol) and, ketoconazole (-6.7 kcal/mol). The common binding affinity amino acids are SER 37, LYS 38, CYS 39, LYS 43, GLU 81 and PHE 85. The top scoring compounds (F1762-0560) has showed interactions with the target protein through hydrogen bonding and stacking interactions, particularly with SER 37, CYS 39, and LYS 43. We further investigated the stability of six ligand-TXNPx complexes over 200 ns. The results indicated good structural stability (RMSD: 0.05-0.20 nm; Rg: 1.45-1.52 nm), with F0556-0242 and F1762-0560 showing the least fluctuations. FDA_461 has the most hydrogen bonds (up to 5), while Ketoconazole was more flexible (RMSD peak: 0.25 nm). These findings suggest that F0556-0242, F1762-0560, and FDA_461 are promising candidates.