Neurodegenerative diseases (NDs) are characterized by progressive neuronal death, leading to cognitive and motor impairments mainly due to the disrupted cellular homeostasis as a result of accumulation of misfolded and aggregated proteins. Heat Shock Proteins (HSPs) are molecular chaperones with crucial role of proteostasis regulation by facilitating proper protein folding, preventing aggregation, and promoting the degradation of damaged proteins. In this chapter, the focus is on exploring the therapeutic potential of these HSPs in mitigating the pathological effects of neurodegenerative diseases. Initial introduction of HSPs, major functioning, and types of HSPs is followed by the focal point of this chapter, i.e., the mechanism of cellular protection and potential correlation in neuroprotection. This chapter also explores the therapeutic implications of HSP modulation in various NDs as well as the major challenges and obstacles in translating HSP-based therapies into clinical practice. Therefore, concluding that HSPs represent a promising therapeutic target for neurodegenerative diseases, offering a multifaceted approach to alleviating disease pathology. HSP modulation is a promising area of research with significant potential for developing novel treatments that could slow or halt the progression of these debilitating disorders.