The development of novel materials with improved radiation shielding capability is a fundamental step towards the optimization of passive radiation countermeasures. Polyethylene (PE) nanocomposites filled with carbon nanotubes (CNT) or graphene nanoplatelets (GNP) can be a good compromise for maintaining the radiation shielding properties of the hydrogen-rich polymer while endowing the material with multifunctional properties. In this work, nanocomposite materials based on medium-density polyethylene (MDPE) loaded with different amounts of multi-walled carbon nanotubes (MWCNT), GNPs, and hybrid MWCNT/GNP nanofillers were fabricated, and their properties were examined before and after proton exposure. The effects of irradiation were evaluated in terms of modifications in the chemical and physical structure, wettability, and surface morphology of the nanocomposites. The aim of this work was to define and compare the MDPE-based nanocomposite behavior under proton irradiation in order to establish the best system for applications as space shielding materials.