Bentonite pellet-based mixtures are currently investigated as candidate materials in large-scale in situ sealing experiments such as the Vertical SEALing project by the Institute for Radiological protection and Nuclear Safety (IRSN, France) due to their expected gap-filling capacity in engineered barrier systems for the geological disposal of radioactive waste. In the short term, after installation, the hydro-mechanical behaviour of these pellet-based structures is governed by pellet-pellet interactions, which have been characterised experimentally by oedometer compression tests and numerically by discrete-element modelling of single-layered pellet skeleton samples. In this work, we integrate these experimental and numerical tools to characterise the compressibility of three-layered pellet-based structures with axis-oriented arrangements. We validate the simulated deformation of bentonite pellet samples against experimental data and analyse the evolution of the dry density distribution and axial stiffness along the oedometer compression curve. Our integrated approach has implications for the emplacement and monitoring in situ tests on multi-layered pellet-based barrier systems.