This chapter covers the various biodegradation mechanisms of nanocellulose scaffolds using microorganisms, enzymes and radiation, where factors like pH, temperature and hydrophobicity play a vital role in the reduction of molecular weight and increase in crystallinity. In vivo and in vitro breakdown procedures are included which can follow the hydrolysis, enzymatic and/or thermal degradation steps. In reactive oxygen species (ROS)-mediated scaffold degradation studies, faster splitting facilitating cell infiltration, resulting in better neovascularisation and engraftment at the implanted site, is observed distinguished by improved swelling ratio, porosity and hydrophilicity. Quantifying methods used for characterisation, like X-ray diffraction, high-performance liquid chromatography, thermogravimetric analysis, nuclear magnetic resonance and others, to identify the typical comparative physicochemical changes in the pristine and degraded nanocellulose structures are explained. These non-destructive techniques allow quantitative assessment and repeated measurement of the same sample which is an added advantage during the degradation process.