This review discusses the role of the neuroimmune system in Alzheimer's disease (AD) and Parkinson's disease (PD), highlighting the complex interactions between neuroinflammation, immune dysregulation, and abnormal protein aggregation. The immune system, particularly microglia, plays a critical role in both diseases, contributing to neuronal loss and symptom exacerbation. Researchers use in vitro and in vivo models, including 2D cultures, animal models, and advanced 3D models and organ-on-a-chip systems, to better understand the pathophysiology of these neurodegenerative diseases. These models offer significant advantages over traditional 2D models, such as improved cell viability, reduced reliance on animal models, and the ability to mimic the complex intracellular environment. The application of 3D and organ-on-a-chip models in neurodegenerative disease research represents a major advancement, providing a more realistic representation of the neuroimmune system's complex interactions. These models are crucial for developing new treatments and understanding the mechanisms underlying AD and PD. The review also explores the role of the immune system in AD and PD, including the impact of neuroinflammation, immune dysfunction, and the involvement of various immune cells such as microglia, macrophages, T cells, and B cells. Current treatments for AD and PD include drugs targeting acetylcholinesterase, monoclonal antibodies, and dopamine agonists, among others. In vitro and in vivo models are essential for studying the neuroimmune system and developing new therapies. The review highlights the importance of 3D models in accurately simulating the complex interactions between the immune system and the nervous system, as well as the potential of these models in drug discovery and disease modeling. The use of invertebrate and vertebrate models, such as fruit flies and mice, has also been explored to study the pathogenesis of AD and PD. Overall, the review emphasizes the importance of understanding the neuroimmune system in AD and PD and the potential of advanced models in developing effective treatments for these debilitating diseases.This review discusses the role of the neuroimmune system in Alzheimer's disease (AD) and Parkinson's disease (PD), highlighting the complex interactions between neuroinflammation, immune dysregulation, and abnormal protein aggregation. The immune system, particularly microglia, plays a critical role in both diseases, contributing to neuronal loss and symptom exacerbation. Researchers use in vitro and in vivo models, including 2D cultures, animal models, and advanced 3D models and organ-on-a-chip systems, to better understand the pathophysiology of these neurodegenerative diseases. These models offer significant advantages over traditional 2D models, such as improved cell viability, reduced reliance on animal models, and the ability to mimic the complex intracellular environment. The application of 3D and organ-on-a-chip models in neurodegenerative disease research represents a major advancement, providing a more realistic representation of the neuroimmune system's complex interactions. These models are crucial for developing new treatments and understanding the mechanisms underlying AD and PD. The review also explores the role of the immune system in AD and PD, including the impact of neuroinflammation, immune dysfunction, and the involvement of various immune cells such as microglia, macrophages, T cells, and B cells. Current treatments for AD and PD include drugs targeting acetylcholinesterase, monoclonal antibodies, and dopamine agonists, among others. In vitro and in vivo models are essential for studying the neuroimmune system and developing new therapies. The review highlights the importance of 3D models in accurately simulating the complex interactions between the immune system and the nervous system, as well as the potential of these models in drug discovery and disease modeling. The use of invertebrate and vertebrate models, such as fruit flies and mice, has also been explored to study the pathogenesis of AD and PD. Overall, the review emphasizes the importance of understanding the neuroimmune system in AD and PD and the potential of advanced models in developing effective treatments for these debilitating diseases.