Abstract: Intestinal flora is an important part of the human intestinal microenvironment, which can interact with the immune, metabolic and nervous systems, and is the basic determinant of multiple physiological and pathological processes of the human body. Gut microbiota metabolites are important links for gut microbiota to regulate body homeostasis, including metabolites produced by gut bacteria decomposing dietary components, metabolites produced by the host and modified by gut bacteria, and metabolites synthesized de novo by gut bacteria. Microgravity, radiation and dietary changes during space flight have a significant impact on the composition and metabolic pathway of intestinal flora, promote the change of intestinal flora, the imbalance of the proportion of Firmicum/Bacteroides, the decrease of beneficial metabolites and the increase of harmful metabolites, and induce the dysfunction of immune, cardiovascular, muscle and bone systems, thus affecting the physiological health of the body. Recent research advances in regulation of intestinal flora and its metabolites by space environment are reviewed in this paper.