Neurodegenerative disorders (NDs) lead to the progressive degeneration of the structural and physiological functions of the central and peripheral nervous systems, resulting in lifelong cognitive and motor dysfunction. Although comprehensive treatment of NDs is lacking, small interfering (si)RNA has shown therapeutic utility in the form of cellular nuclease-driven downregulation of mRNA levels. Various nanotechnologies have been used to modulate crucial physicochemical and biopharmaceutical properties of siRNA to provide protection and to enhance biomembrane interactions, residence times, tissue absorption, and cellular internalization for improved cytoplasm and/or nucleus interactions. In this review, we highlight advances in, and the role of, siRNA-based nanocarriers for the treatment of various NDs.