Xyloglucan (XG) is a cellulosic backbone polysaccharide commercially used for food applications, but also widely investigated in biomedical applications, for its gelling properties and specific biological activity. In this study, the possibility of using gamma radiation to cleave XG and generate lower molecular weight variants was explored. The impact of absorbed dose and irradiation conditions on the XG molecular weight distribution was investigated. Two other cellulosic polysaccharides, hydroxypropyl cellulose (HPC) and an oxidized variant of XG (CXG), were also studied for comparison. Before irradiation, the polymers were characterized with thermal gravimetric analysis and, after irradiation, with gel permeation chromatography. The results showed that for XG irradiated in dilute aqueous solution, a dose of 10 Gy is sufficient to significantly reduce the polymer molecular weight, while HPC is less affected by irradiation under identical conditions. When the polymers were irradiated in the solid form, either dry or humid, the reduction in average molecular weight is much less pronounced. Interestingly, for HPC the cleavage of the chains is more pronounced for the dry than for the humid powder. A similar behavior, but less pronounced, was observed for XG and CXG. Arguably, when water was present in the system as bound water it had a protective effect. This is probably due to energy transfer from the polymer to the bound water preventing chain scission. Indeed, humid HPC has more bound water than XG and CXG. Conversely, when water was present as solvent, water radiolysis products were able to efficiently induce depolymerization. Graphical abstract: [Figure not available: see fulltext.].