Membrane technology has been widely employed for seawater desalination, water and wastewater reclamation, while membrane fouling still remains as a major challenge. The polysaccharides in extracellular polymeric substances (EPS) have been recognized as an important foulant that causes serious membrane fouling, while the detailed structure of polysaccharides and the intermolecular interactions between them have not been adequately disclosed. In this study, two different polysaccharides and their mixtures were used to study the intermolecular cross-linking of polysaccharides as well as its effects on membrane fouling. Results demonstrated that the fouling propensities of distinct polysaccharides were completely different, which was attributed to the different intermolecular interactions lying in polysaccharides. The cross-linking among molecules of polysaccharide, regardless of the homogeneity, was found to form complex networks and determine the effective dimension of polysaccharides. Depending on the effective dimension of foulants, pore blocking and cake layer occurred subsequently during filtration processes. In light of this, it potentially gives new insights into the fouling behaviours by combining the structure-function knowledge of polysaccharides with their fouling propensity. In addition, transparent exopolymeric particles (TEP) measurement was found to provide an intuitionistic evaluation of the complex networks formed from polysaccharides, so that may act as a good indicator of fouling during membrane filtration. Copyright © 2018 Elsevier Ltd. All rights reserved.