 The study aimed to screen natural compounds against the BDNF variant, V66M, which affects memory, cognition, and mooned regulation, using multiple tools like Autodocvena, Biovia Discovery Studio, PyMOL, CbDoc, ImodServer, SwissADMT, and SwissPredictLigansTarget. The compounds vitamin D3, curcumin, vitamin C, and quacetin with binding energies values of 5.5, 6.1, 4.5, and 6.7 kW per mole, respectively, were selected as ligands that bind to the active sites of the BDNF variant, V66M, biohydrophobic bonds, hydrogen bonds, and electrostatic interactions. The ADMET analysis revealed that the ligands exhibited sound pharmacokinetic and toxicity profiles. An MD simulation study showed that quacetin formed a more structurally stable complex with the target protein and was determined to be a more potent BDNF variant, V66M, inhibitor. This article was authored by Isra Sakawot, Muhammad Amakan, Rehma Rehman, and others. We are article.tv, links in the description below.