Mitochondrial function is critical for intestinal health and is disrupted in gastrointestinal diseases such as inflammatory bowel disease (IBD) and colorectal cancer (CRC). Mitochondria in intestinal epithelial cells (IECs) regulate energy metabolism, signaling, and cellular homeostasis, and their dysfunction contributes to disease pathogenesis. IBD is associated with altered IEC mitochondrial function, including impaired electron transport chain (ETC) activity and reduced expression of genes involved in mitochondrial function. CRC arises from genetic mutations in pathways such as APC–KRAS–p53 and BRAF–MLH1 hypermethylation, with mitochondrial dysfunction playing a role in disease progression. Mitochondrial dysfunction in IECs is linked to epithelial barrier impairment, gut microbiota dysbiosis, and chronic inflammation. Mitochondrial-targeted therapies are being explored for IBD and CRC, with a focus on restoring mitochondrial function and reducing oxidative stress. Mitochondrial ROS (reactive oxygen species) serve both beneficial and harmful roles in signaling, with excessive ROS contributing to cellular damage and inflammation. Mitochondrial dysfunction also affects epigenetic regulation, influencing gene expression and cellular metabolism. In IBD, mitochondrial dysfunction is associated with altered mitochondrial metabolism, epigenetic changes, and dysbiosis of the gut microbiota. In CRC, mitochondrial dysfunction contributes to tumor metabolism and heterogeneity, with implications for treatment response. Mitochondrial quality control mechanisms, including mitophagy and fission, are essential for maintaining mitochondrial health and preventing disease. Targeting mitochondrial dysfunction offers potential therapeutic strategies for IBD and CRC, with ongoing research exploring mitochondrial-targeted therapies and the role of mitochondrial dysfunction in disease progression.Mitochondrial function is critical for intestinal health and is disrupted in gastrointestinal diseases such as inflammatory bowel disease (IBD) and colorectal cancer (CRC). Mitochondria in intestinal epithelial cells (IECs) regulate energy metabolism, signaling, and cellular homeostasis, and their dysfunction contributes to disease pathogenesis. IBD is associated with altered IEC mitochondrial function, including impaired electron transport chain (ETC) activity and reduced expression of genes involved in mitochondrial function. CRC arises from genetic mutations in pathways such as APC–KRAS–p53 and BRAF–MLH1 hypermethylation, with mitochondrial dysfunction playing a role in disease progression. Mitochondrial dysfunction in IECs is linked to epithelial barrier impairment, gut microbiota dysbiosis, and chronic inflammation. Mitochondrial-targeted therapies are being explored for IBD and CRC, with a focus on restoring mitochondrial function and reducing oxidative stress. Mitochondrial ROS (reactive oxygen species) serve both beneficial and harmful roles in signaling, with excessive ROS contributing to cellular damage and inflammation. Mitochondrial dysfunction also affects epigenetic regulation, influencing gene expression and cellular metabolism. In IBD, mitochondrial dysfunction is associated with altered mitochondrial metabolism, epigenetic changes, and dysbiosis of the gut microbiota. In CRC, mitochondrial dysfunction contributes to tumor metabolism and heterogeneity, with implications for treatment response. Mitochondrial quality control mechanisms, including mitophagy and fission, are essential for maintaining mitochondrial health and preventing disease. Targeting mitochondrial dysfunction offers potential therapeutic strategies for IBD and CRC, with ongoing research exploring mitochondrial-targeted therapies and the role of mitochondrial dysfunction in disease progression.