Fouling behaviors of polysaccharides vary with their structure, while the mechanisms underlying this phenomenon remain unexplored. This work was carried out to explore the thermodynamic fouling mechanisms of polysaccharides with different structure. Carrageenan and xanthan gum were selected as the model polysaccharides with structure of straight and branch chains, respectively. Batch filtration experiments showed that xanthan gum solution corresponded to a more rapid flux decline trend, and specific filtration resistance (SFR) of xanthan gum (2.32 × 1015 m−1 kg−1) was over 10 times than that of carrageenan (2.21 × 1014 m−1 kg−1). It was found that, xanthan gum possessed a more disordered structure and a rather higher viscosity (15.03 mPa·s V.S. 1.98 mPa·s for carrageenan). Calculation of extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory showed higher adhesion energy of xanthan gum (−42.82 my m−2 V.S. −23.26 mJ m−2 for carrageenan). Scanning electron microscopy (SEM) analyses showed that xanthan gum gel layer had a more homogenous structure and rigid polymer backbone, indicating better mixing with water to form a gel. As verified by heating experiments, such a structure tended to contain more bound water. According to this information, Flory-Huggins lattice theory was introduced to build a bridge between polymeric structure and SFR. It was revealed that branch structure corresponded to higher chemical potential change during gel layer formation, and higher ability to carry bound water, resulting in higher filtration resistance during filtration process. This work revealed the fundamental thermodynamic mechanism of membrane fouling caused by polysaccharides with different structure, deepening understanding of membrane fouling. Display omitted •Specific filtration resistance (SFR) of xanthan gum was about 10 times than that of carrageenan.•Molecular structure contributed to higher adhesion energy of xanthan gum to membrane surface.•Gel formation of xanthan gum corresponded to higher chemical potential change and SFR.•Thermodynamic mechanisms governed polysaccharides' adhesion and gel layer filtration process.