Cardanol(3-pentadecenyl-phenol) is a well-known non-edible natural oil derived from Cashew Nutshell Liquid and represents a valid alternative to petro-based derivatives (e.g. nonylphenol) as a protective group (blocking agent) for isocyanates. In fact, once used in polyurethane prepolymers, this substance demonstrates various benefits including favorable deblocking conditions, lower viscosity, and excellent storage stability in comparison to commonly used phenolic compounds. One of the most known deblocking methods involves the exposure to elevated temperatures, typically around 150 °C –200°C. However, not all substrates (e.g. plastics) and applications can tolerate such high temperatures, therefore the possibility to optimize the deblocking conditions can be a valuable tool to further expand the applicability of cardanol as a sustainable, eco-friendly polyurethane prepolymers’ blocking agent. In this Paper, different approaches to tune deblocking conditions will be investigated, like the use of catalysts, deblocking agents (e.g. amines, polyols), and chemical modification of cardanol aromatic ring by nitration, to introduce electron withdrawing groups. Model cardanol-blocked substrates will be synthesized starting from commercially available isocyanates (both aromatic and aliphatic) and polymeric diols, subsequently characterized for their thermal behaviorby Different Scanning Calorimetry (DSC).