Neurodegenerative disease (ND) is a complex concept involves multiple pathogenesis including neuronal demyelination, apoptosis under oxidative stress, neuroinflammation with further cortical and spinal atrophy, which may lead to cognition impairment and multiple neural dysfunctions. It may present as a chronic and irreversibly progressive disorder and shows the common pathological pictures among its various types including Alzheimer's disease (AD), Parkinson's disease (AD), Huntington's disease (HD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). The symptoms often occur among the elderly above 50 years old and last from years to decades. Such facts lead ND as the highest priority to geriatrics and its related medical care. Due to its chronic progressively characteristics, regularly invasive procedure arrangements may face the difficulty and regarded as unbearable in the clinical practice. Unfortunately, current available therapy is mainly on symptom relief and the potential therapeutic targets may focus on the macromolecules including oligomer, peptides, or even functional proteins with the quaternary structure since multiple proteinopathy involvement in ND pathogenesis. Such macromolecular administrations cause the challenges in the routine drug delivery selections due to the impossibility of the traditional oral intake.Intra-maxillary molecular releasing is a newly drug delivery pathway via dental implant and may directly reach the inside bone marrow. It presents the advantages in long-term and continuous macromolecular releasing with relative painless process, which is appropriate for further applications in ND therapeutics. The stability of dental implant inside the oral cavity has also been proved for decades among more than millions around the world. However, such delivery pathway is currently under development and further interdisciplinary investigations are needed including therapeutics, pharmacokinetics, neurology, molecular biology, clinical dentistry, chemical engineering, automatics and further complementary metal-oxidesemiconductor (CMOS) technology to ensure the efficiency and prove the safety concern.