Nanosize hydrogels (nanogels) are polymer nanoparticles with three-dimensional networks formed by chemical and/or physical cross-linking of polymer chains. We reported for the first time physically cross-linked nanogels by self-assembly of amphiphilic polysaccharides in water. Biomedical applications of nanogels have made rapid progress in the last 10 years. A current challenge is the development of strategies for the delivery of more fragile drugs such as proteins which are easily unfolded or inactivated under physiological conditions. To overcome this issue, the chaperone-like function of the polysaccharide nanogels is an important concept that can lead to breakthroughs in the effective delivery of proteins. Here, we report recent progress in polysaccharide nanogel engineering for protein delivery.