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Microgravity, as an unfavorable abiotic environment, may lead to changes in cell growth and metabolism. Glycogen and extracellular polysaccharide are the main forms of the intra- and extracellular carbohydrate metabolites of cyanobacteria cells. In this study, we used a 2-D clinostat to simulate microgravity, to analyze the molecular regulation of basic sugar metabolism products in cyanobacteria. During the 20 days of clinorotation, the contents of reserved glycogen and exopolysaccharide (EPS) and the transcriptional expression of related genes such as glgP (glycogen phosphorylase), epsB (exopolysaccharide transport protein), and exoD (exopolysaccharide synthesis protein) of Synechocystis sp. PCC6803 were detected. Results showed that glycogen decreased significantly during the whole period of clinorotation, while EPS increased compared with the ground control. Gene expression analysis showed that the glgP gene which regulated degradation of glycogen was induced during clinorotation, thereby providing more substances for EPS synthesis. The EPS synthesis protein gene exoD was depressed at the early stage of clinorotation, induced in the middle phase, and depressed again in the late phase. The EPS transportation protein gene epsB was depressed in the middle phase but induced at the early and late phases. It showed that the synthesis and transportation of EPS was regulated by exoD and epsB on the transcriptional level. The study was the first time to analyze the molecular mechanism on EPS biosynthesis and transportation under simulated microgravity condition. Our results not only help us to better understand the adaptive mechanism of cyanobacteria in space but also provide a basis for the local control of desert sands in enclosed space in future.