Hydrogels have existed for more than half a century and today they find many applications in many materials of common use and in various processes ranging from industrial to biological. They are a unique class of cross-linked polymers that are able to adsorb a large amount of water while preserving their three-dimensional structure. Among the wide range of polymeric formulation that gives rise to biocompatible hydrogels, an attractive class of ‘intelligent gels’ is represented by stimuli-responsive hydrogels. They are polymeric materials whose swelling behaviour, network structure, permeability or mechanical strength can be triggered in response to different stimuli, such as temperature, pH and ionic strength. The recently growing use of hydrogels especially in technological fields of high social impact has led to the need of the systematic exploration of the strict relationship between the molecular properties and the macroscopic behaviours observed in pH-responsive hydrogels. The understanding of the fundamental properties of these complex systems can benefit from a joint use of different experimental techniques that provides a multi-scale view -from molecular to macroscopic length scale- of the pH-sensitive gelling behaviour exhibited by hydrogels. In this contribution, we show how the joint combination of UV Resonant Raman (UVRR) and Brillouin light scattering (BLS) measurements together with Small Angle Neutron Scattering (SANS) experiments can be successfully implemented to link the static and dynamical features of polysaccharide hydrogels with their water-retaining ability and with their structural and chemical-physical response to pH variations. Moreover, we discuss how the chemical and physical interactions between the drug and the hydrophobic/hydrophilic moieties of polymer matrix can change the hydrogel characteristics influencing the release performances. As prototype case study, the water adsorption properties and the pH-responsive behaviour exhibited by natural and biodegradable cyclodextrin-based hydrogels, namely cyclodextrin nanosponges (NS) will be explored.