Abstract: It was found that intestinal flora could directly regulate mitochondria of intestinal epithelial cells or indirectly through the nucleus. This effect is associated with the flora metabolites such as short-chain fatty acids (SCFAs), hydrogen sulfide (H₂S) and nitric oxide (NO). These metabolites are involved in mitochondria-related energy metabolic processes and the production of mitochondrial reactive oxygen species (mtROS), and even in the immune response of the whole organism. Numerous studies have also shown that intestinal flora metabolites and mitochondria have become a hot spot for research on the mechanism of action of traditional Chinese medicine, but the research on the mechanism of association between them is not yet in-depth. In this review, we summarize the mechanism of mitochondrial regulation of intestinal epithelial cells by intestinal flora metabolites and herbal interventions to provide a theoretical basis for targeting intestinal microbes and mitochondria to regulate body metabolism and health.