Lipopolysaccharides from the commensal gut‐associated microbiota are interesting biomolecules for the treatment of various inflammatory diseases. Different from pathogenic lipopolysaccharides, commensal lipopolysaccharides have distinct chemical structures and mediate beneficial homeostasis with the immune system of host. However, the accessibility issues of homogenous and pure commensal lipopolysaccharides hampered the in‐depth studies of their functions. In this concept article, we highlight the recent synthesis of lipopolysaccharides from gut‐associated lymphoid‐tissue‐resident Alcaligenes faecalis and Bacteroides vulgatus, which hopes to inspire the more efforts devoting to this fantastic biomolecules.