Vitamin A plays essential roles in nervous system development but is increasingly recognized to perform key functions in the adult brain including support of neuronal health as well as maintenance of synaptic plasticity. Insufficiency has been linked to the pathogenesis of neurodegenerative diseases, particularly motor-related neurodegenerative diseases and cognitive and dementia-related neurodegenerative disorders. Through its active metabolite, retinoic acid (RA), vitamin A regulates the expression of genes critical for neuronal survival, axonal growth, and neurotransmission. Disruption of RA signaling pathways has been associated with increased vulnerability of motor neurons to oxidative stress, inflammation, excitotoxicity, and pathological stress granule (SG) formation, key mechanisms implicated in neuronal and motor neuron degeneration. Emerging evidence from both preclinical and clinical studies suggests that vitamin A deficiency (VAD) may contribute to disease onset and progression by impairing proteostasis and neuroprotective mechanisms, and disrupting central nervous system homeostasis. These findings underscore the potential importance of vitamin A and its signaling pathways in motor-related neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) and support continued investigation into nutritional and vitamin A-based interventions as potential therapeutic strategies. The following chapter reviews the potential therapeutic applications of vitamin A and its active metabolite, RA, in neurodegenerative diseases, with a specific focus on motor-related neurodegenerative disorders.