The review explores the connection between the intestinal flora, the kynurenine pathway (KP), neuronal excitotoxicity, and mitochondrial oxidative stress. The KP is a metabolic pathway that processes tryptophan (Trp) into various metabolites, including kynurenic acid (KYNA) and quinolinic acid (QUIN), which have significant roles in neurological and mitochondrial disorders. The intestinal microbiota influences KP metabolite production, which in turn affects brain function and mitochondrial health. The review highlights the role of the gut microbiota in regulating Trp availability, which is essential for the synthesis of serotonin and KP metabolites. The KP is involved in various diseases, including mitochondrial disorders, neurodegenerative conditions, and psychiatric disorders. The review discusses the impact of KP metabolites on mitochondrial function, oxidative stress, and neuroinflammation. It also examines the potential therapeutic applications of KP metabolites in treating mitochondrial and neurodegenerative diseases. The study emphasizes the importance of understanding the gut microbiota's role in KP metabolism and its implications for health and disease. The review concludes that the gut microbiota plays a crucial role in the pathophysiology of mitochondrial disorders and that targeting the KP could offer new therapeutic strategies for these conditions.The review explores the connection between the intestinal flora, the kynurenine pathway (KP), neuronal excitotoxicity, and mitochondrial oxidative stress. The KP is a metabolic pathway that processes tryptophan (Trp) into various metabolites, including kynurenic acid (KYNA) and quinolinic acid (QUIN), which have significant roles in neurological and mitochondrial disorders. The intestinal microbiota influences KP metabolite production, which in turn affects brain function and mitochondrial health. The review highlights the role of the gut microbiota in regulating Trp availability, which is essential for the synthesis of serotonin and KP metabolites. The KP is involved in various diseases, including mitochondrial disorders, neurodegenerative conditions, and psychiatric disorders. The review discusses the impact of KP metabolites on mitochondrial function, oxidative stress, and neuroinflammation. It also examines the potential therapeutic applications of KP metabolites in treating mitochondrial and neurodegenerative diseases. The study emphasizes the importance of understanding the gut microbiota's role in KP metabolism and its implications for health and disease. The review concludes that the gut microbiota plays a crucial role in the pathophysiology of mitochondrial disorders and that targeting the KP could offer new therapeutic strategies for these conditions.