Neurodegenerative disorders (NDDs) are a group of diseases characterized by progressive degeneration of the structure and function of the nervous system. These disorders typically result in a gradual decline in cognitive function, movement, and other neurological functions, leading to significant disability and reduced quality of life. Maintaining proteostasis is the essential aspect for normal cellular functioning and overall well-being. However, the intricate balance of protein synthesis, folding, trafficking, and degradation in the cells is impaired and has been implicated in the plethora of multiple health issues like neurodegenerative disorders, cancer, oxidative stress, and other metabolic syndromes. Protein aggregate markers are the classic hallmark and critical indicators for early conditions like Alzheimer’s (AD), Parkinson’s (PD), and Huntington’s disease (HD). Additionally, the understanding of chaperones, proteases, autophagic activity markers, and ubiquitin-proteasome system (UPS) also offers the understanding of the molecular mechanisms underlying protein dysfunction in neurodegenerative diseases. In this chapter, a review of biomarkers for proteostasis alterations, along with the role of oxidative stress contributing to the onset and development of neurodegenerative diseases, is discussed. These biomarkers hold significant potential for improving disease diagnosis, monitoring disease progression, and developing targeted therapies for proteostasis-related disorders.