Transposable elements (TEs) constitute a large part of the genome and are increasingly recognized for their contribution to age-related neurodegeneration. TEs are typically silenced through epigenetic and RNA-based mechanisms. However, with age, repression mechanisms can falter, leading to aberrant TE activation and potentially contributing to the pathogenesis of neurodegenerative diseases (NDs). There is increasing evidence that aberrant activation of TEs contributes to several prominent features of neurodegenerative diseases (NDs), including genomic instability, mitochondrial dysfunction, inflammation, impaired autophagy, and telomere attrition. TE mobilization and resulting de novo insertions can disrupt neuronal gene regulation globally, adversely affecting mitochondrial function and autophagy pathways. In turn, the genomic instability and mitochondrial damage induced by these disruptions may further exacerbate TE activation, creating a detrimental feedback loop. Also, TE-derived double-stranded RNA, double-stranded DNA, and RNA::DNA hybrids can trigger the innate immune response. Aberrant TE activation has been observed in several NDs, such as Alzheimer’s disease (AD), amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD), Parkinson’s disease (PD), and Huntington’s disease (HD). Therefore, targeting TE mobilization pathways could represent a promising therapeutic avenue for mitigating ND progression.