An intriguing feature of infrared (IR) spectroscopy is its capacity to accurately identify and characterize disease morphologies. It enables identification of molecular alterations in wide variety of physiological samples, including but not limited to isolated cellular specimens, body fluid samples and tissue biopsies without the need of using any external agents. Therefore, we aimed to summarize the recent findings on the uses of Fourier Transform IR (FTIR) spectroscopy in assessing the molecular alterations associated with neurodegenerative diseases, a specific group of diseases characterized by progressive and irreversible loss of neuronal cells. In this review, we focus on two specific disease situations, Multiple Sclerosis and Alzheimer's disease, mainly due to the urgent need for identification of a reliable biomarker for their diagnosis. Body fluids, indeed, are very suitable specimens to be used in diagnosis, since they can be easily collected from patients and can accurately reflect biochemical changes. Precise identification of alterations in the molecular profile of body fluid samples from control and affected samples can enable us to identify biomarkers in the diagnosis of aforementioned diseases, and possibly as a crucial clue for developing therapeutical strategies. In this regard, we would like to present current advances in the use of FTIR spectroscopy along with various analysis tools, such as hierarchical cluster analysis (HCA), principal component analysis (PCA). Finally, we present the application of these techniques in Multiple Sclerosis and Alzheimer's disease.