Mitochondrial dysfunction and neuroinflammation are key factors in neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). These diseases are characterized by progressive neuronal cell death and the accumulation of pathological proteins, often accompanied by chronic neuroinflammation. Recent research suggests that mitochondrial dysfunction can both initiate and exacerbate neuroinflammation, contributing to the progression of NDs. Mitochondria are essential for cellular energy production and maintain homeostasis by regulating calcium levels, reactive oxygen species (ROS), and apoptosis. Dysfunction in mitochondria leads to oxidative stress, impaired energy production, and disrupted cellular processes, which can trigger neuroinflammation. Neuroinflammation, in turn, can further damage neurons through the activation of inflammasomes, such as the NLRP3 inflammasome, which produces pro-inflammatory cytokines and contributes to neuronal death. The interplay between mitochondrial dysfunction and neuroinflammation is complex, with each influencing the other in a vicious cycle. Understanding this relationship is crucial for developing therapeutic strategies targeting both mitochondrial health and neuroinflammation. Targeting mitochondrial dysfunction or inflammasome activation has shown promise in preclinical models of NDs, suggesting potential avenues for treatment. However, the exact role of mitochondrial dysfunction as a primary cause or secondary consequence of neurodegeneration remains debated. This review highlights the importance of addressing both mitochondrial health and neuroinflammation in the treatment of NDs.Mitochondrial dysfunction and neuroinflammation are key factors in neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). These diseases are characterized by progressive neuronal cell death and the accumulation of pathological proteins, often accompanied by chronic neuroinflammation. Recent research suggests that mitochondrial dysfunction can both initiate and exacerbate neuroinflammation, contributing to the progression of NDs. Mitochondria are essential for cellular energy production and maintain homeostasis by regulating calcium levels, reactive oxygen species (ROS), and apoptosis. Dysfunction in mitochondria leads to oxidative stress, impaired energy production, and disrupted cellular processes, which can trigger neuroinflammation. Neuroinflammation, in turn, can further damage neurons through the activation of inflammasomes, such as the NLRP3 inflammasome, which produces pro-inflammatory cytokines and contributes to neuronal death. The interplay between mitochondrial dysfunction and neuroinflammation is complex, with each influencing the other in a vicious cycle. Understanding this relationship is crucial for developing therapeutic strategies targeting both mitochondrial health and neuroinflammation. Targeting mitochondrial dysfunction or inflammasome activation has shown promise in preclinical models of NDs, suggesting potential avenues for treatment. However, the exact role of mitochondrial dysfunction as a primary cause or secondary consequence of neurodegeneration remains debated. This review highlights the importance of addressing both mitochondrial health and neuroinflammation in the treatment of NDs.