Abstract <p>Macroporous cryogels with and without the additives of chaotropic and kosmotropic substances (urea, guanidine hydrochloride, trehalose, and hydroxyproline) were prepared by freezing a 100 g/L aqueous solution of poly(vinyl alcohol) (PVA) at—20°C, maintaining it at this temperature for 12 h, and then thawing it while heating at a rate of 0.03°C/min. Also, these chaotropic and kosmotropic substances were introduced into the PVA cryogel matrix without additives by saturating the gel materials in the respective aqueous solutions. These same substances were added by saturating the gel materials in the corresponding aqueous solutions. The character of changes in the physicochemical parameters of PVA cryogels formed in the presence of lyotropic agents and PVA cryogels after saturation of the gel samples in the water solutions of these substances was studied. It was shown that chaotropic substances negatively affect the elasticity and heat endurance of the resulting materials, while the presence of kosmotropic additives in the cryogel matrix leads to its strengthening and increased thermal stability. Moreover, this effect is observed for both options of introducing low-molecular-weight substances into the cryogel matrix—when adding additives to the initial polymer solution before cryogenic processing and when incorporation of the same additives to the samples via saturation. However, for chaotropic substances, the saturation method allows for a significant increase in the working concentration of these substances while maintaining the elastic properties of the materials. Taking into account that PVACGs are used as carriers of low-molecular-weight water-soluble substances in various applied fields (medicine, biotechnology, art restoration, etc.), the obtained research results are of not only scientific but also of practical interest.</p>