Neurodegenerative diseases encompass a variety of conditions, among which Alzheimer’s disease (AD) is a notable example. AD is an incurable, age-related neurodegenerative disorder characterized by irreversible cognitive impairments and neuronal damage. Consequently, the identification of potential biomarkers prior to the deposition of amyloid-β plaques is critical for the early intervention of AD. Multiple sclerosis (MS) is another chronic autoimmune demyelinating disorder affecting the central nervous system, which poses challenges for early diagnosis. Similarly, Parkinson’s disease (PD) is a neurodegenerative condition that is often difficult to diagnose before the onset of clinical symptoms and pathological alterations. Urine, lacking homeostatic regulation, may reflect systemic changes associated with AD, MS, and PD earlier than cerebrospinal fluid or blood. This chapter focuses on candidate urinary biomarkers for the early detection of AD prior to amyloid-β plaque deposition in the APP (swe)/PSEN1dE9 transgenic mouse model, for the identification of MS during the early stages of clinical manifestation in an experimental autoimmune encephalomyelitis (EAE) rat model, and for the discovery of potential biomarkers preceding significant behavioral and pathological changes in PD. In the study, 29 urinary proteins exhibited alterations in 4-month-old APP (swe)/PSEN1dE9 transgenic mice, which had not yet begun to deposit amyloid-β plaques; of these, 15 proteins have been previously associated with AD, while 9 have been identified as biomarkers for the disease. In the seven-day EAE rat model, 31 urinary proteins were found to be altered, with 17 of these linked to neurological functions. Additionally, two differential proteins were identified at 4 months prior to any notable behavioral or pathological changes, with one protein specifically associated with PD.