Changes in the molecular weight characteristics of polysaccharide macromolecules - arabinogalactan, hydroxyethyl starch 200/0.5, Fibregum, and dextrans 10, 40, and 70 - were studied during mechanochemical processing. A preference for “gentle” conditions for mechanical processing (~1 g) were established, as these conditions do not lead to destruction of polysaccharide macromolecules. An additional advantage of these mechanical processing regimes is that they can be scaled up to industrial flow mills. Mechanochemical processing had no adverse effect on the toxicity measures of the polysaccharides studied. Toxicological studies of mechanically processed arabinogalactan, hydroxyethyl starch 200/0.5, Fibregum, and dextrans 10, 40, and 70 showed that these polysaccharides and the products of their mechanochemical processing can be classified as class 4 (low-toxicity) substances.