Exploring the nature of histidine residue tautomerization via a systematic conformational study is essential for understanding the pathology and toxicity of several neurodegenerative diseases, as well as for their diagnosis and treatment. Herein, density functional theory (DFT) calculations were used to determine the Tau protein's histidine-containing dipeptide (Lys-His, His-Gln, and His-Val) and tripeptide (Lys-His-Gln and Lys-His-Val) isomeric conformations via intramolecular hydrogen bond interactions, with particular attention to the influence of N-H group isomeric forms on their properties. The calculated infrared (IR) spectroscopy of the N-H stretch region of each isomer and nuclear magnetic resonance (NMR) shielding of the imidazole ring carbon atoms (