||Two dimensional (2D) transition metal dichalcogenides (TMDs) gain increased attention due to their outstanding optical properties. For the development of biosensors based on TMDs’ optical properties, it is required to effectively exfoliate and functionalize TMDs in an aqueous solution. Herein, we report a successful strategy for the simultaneous exfoliation and functionalization of TMD nanosheets with a biocompatible polymer, dextran, in water. The multivalent hydrogen bonding between the hydroxyl groups of dextran and the chalcogen atoms of the TMD nanosheets facilitated their exfoliation and functionalization in water through simple sonication. The resulting dextran/TMD nanosheet hybrid showed a higher affinity to Escherichia coli O157:H7 than antibodies and aptamers, allowing the selective and sensitive detection of E. coli without the use of antibodies.