The article reviews the interplay between mitochondrial dysfunction and neuroinflammation in the development and progression of neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). It highlights that while NDs have distinct clinical manifestations and underlying mechanisms, they share common pathological features, including defective protein homeostasis and mitochondrial dysfunction. Mitochondrial dysfunction can lead to oxidative stress, ER stress, neuroinflammation, and other cellular dysfunctions, which in turn contribute to the activation of neuroinflammatory responses. The review discusses the role of inflammasomes, particularly the NLRP3 inflammasome, in mediating this inflammatory response. It also explores the potential therapeutic targets that could be developed to address the interplay between mitochondrial dysfunction and neuroinflammation, such as targeting mitochondria homeostasis or inflammasome activation. The authors conclude by emphasizing the need for a deeper understanding of the complex interactions between these processes to develop effective treatments for NDs.The article reviews the interplay between mitochondrial dysfunction and neuroinflammation in the development and progression of neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). It highlights that while NDs have distinct clinical manifestations and underlying mechanisms, they share common pathological features, including defective protein homeostasis and mitochondrial dysfunction. Mitochondrial dysfunction can lead to oxidative stress, ER stress, neuroinflammation, and other cellular dysfunctions, which in turn contribute to the activation of neuroinflammatory responses. The review discusses the role of inflammasomes, particularly the NLRP3 inflammasome, in mediating this inflammatory response. It also explores the potential therapeutic targets that could be developed to address the interplay between mitochondrial dysfunction and neuroinflammation, such as targeting mitochondria homeostasis or inflammasome activation. The authors conclude by emphasizing the need for a deeper understanding of the complex interactions between these processes to develop effective treatments for NDs.