AbstractChitosan and its highly hydrophilic 1‐deoxy‐lactit‐1‐yl derivative (Chitlac) are polysaccharides with increasing biomedical applications. Aimed to unravel their conformational properties we have performed a series of molecular dynamics simulations of Chitosan/Chitlac decamers, exploring different degrees of substitution (DS) of lactitol side chains. At low DS, two conformational regions with different populations are visited, while for DS ≥ 20% the oligomers remain mostly linear and only one main region of the glycosidic angles is sampled. These conformers are (locally) characterized by extended helical “propensities”. Helical conformations 32 and 21, by far the most abundant, only develop in the main region. The accessible conformational space is clearly enlarged at high ionic strength, evidencing also a new region accessible to the glycosidic angles, with short and frequent interchange between regions. Simulations of neutral decamers share these features, pointing to a central role of electrostatic repulsion between charged moieties. These interactions seem to determine the conformational behavior of the chitosan backbone, with no evident influence of H‐bond interactions. Finally, it is also shown that increasing temperature only slightly enlarges the available conformational space, but certainly without signs of a temperature‐induced conformational transition.