The human gut microbiota, a complex polymicrobial ecosystem, plays a crucial role in health and disease. Lachnospiraceae, a core component of the gut microbiota, colonizes the intestinal lumen from birth and increases in species richness and relative abundance throughout life. While members of Lachnospiraceae are significant producers of short-chain fatty acids (SCFAs), different taxa within this family are also associated with various intra- and extraintestinal diseases. The impact of Lachnospiraceae on host physiology is inconsistent across studies. This review discusses the changes in Lachnospiraceae abundances in health and disease, and explores how host diet influences their growth and how their metabolites affect host physiology. Lachnospiraceae are anaerobic, fermentative, and chemoorganotrophic bacteria that can degrade complex carbohydrates and produce SCFAs such as acetate, propionate, and butyrate. These SCFAs have beneficial effects on host health, including modulating the immune system, improving gut integrity, and regulating metabolism. However, certain Lachnospiraceae taxa are associated with metabolic diseases, liver diseases, inflammatory bowel disease, and chronic kidney disease. The diet significantly modulates Lachnospiraceae diversity, with complex diets providing a range of growth-promoting and inhibiting factors for specific phylotypes. Understanding the mechanisms of interactions between Lachnospiraceae and the host, particularly the role of diet, is essential for developing microbial-targeted therapies to prevent and treat intestinal and extraintestinal diseases.The human gut microbiota, a complex polymicrobial ecosystem, plays a crucial role in health and disease. Lachnospiraceae, a core component of the gut microbiota, colonizes the intestinal lumen from birth and increases in species richness and relative abundance throughout life. While members of Lachnospiraceae are significant producers of short-chain fatty acids (SCFAs), different taxa within this family are also associated with various intra- and extraintestinal diseases. The impact of Lachnospiraceae on host physiology is inconsistent across studies. This review discusses the changes in Lachnospiraceae abundances in health and disease, and explores how host diet influences their growth and how their metabolites affect host physiology. Lachnospiraceae are anaerobic, fermentative, and chemoorganotrophic bacteria that can degrade complex carbohydrates and produce SCFAs such as acetate, propionate, and butyrate. These SCFAs have beneficial effects on host health, including modulating the immune system, improving gut integrity, and regulating metabolism. However, certain Lachnospiraceae taxa are associated with metabolic diseases, liver diseases, inflammatory bowel disease, and chronic kidney disease. The diet significantly modulates Lachnospiraceae diversity, with complex diets providing a range of growth-promoting and inhibiting factors for specific phylotypes. Understanding the mechanisms of interactions between Lachnospiraceae and the host, particularly the role of diet, is essential for developing microbial-targeted therapies to prevent and treat intestinal and extraintestinal diseases.