Ionizing radiations, commonly applied as diagnostic tools in Cultural Heritage (CH) field, are also proving effective for eliminating biodeteriogens (insects, fungi, bacteria and molds) responsible for the degradation of CH artifacts and often harmful for restorers, archivists and librarians. The use of ionizing radiations, such as gamma rays, for CH treatments is spreading in many countries. However, some CH operators remain resistant due to insufficient knowledge about the potential physico-chemical modifications (secondary effects) induced by radiation. This work aims to investigate and compare the effects of irradiation parameters (such as absorbed dose and dose rate) on old paper samples and new pure-cellulose paper, chosen as a reference model material. Absorbed doses up to 8 kGy have been used, as these values are commonly agreed upon for the preservation treatment of CH artifacts and are generally effective for biodeteriogens removal. Optimizing irradiation conditions helps to minimize secondary effects (such as oxidation, depolymerization or color changes), thereby increasing the reliability of the process and boosting confidence among CH operators. The secondary effects were analyzed using various physico-chemical characterizations (Fourier Transform Infrared spectroscopy, Raman microscopy, viscosimetric and colorimetric analysis) on old and new paper samples. The results indicate varying behaviors, correlated with paper composition, sample age and irradiation parameters, towards gamma radiation. This groundbreaking study not only confirms the efficacy of gamma irradiation treatments but also provides essential data that will aid in the development of optimized best practice protocols and guidelines for non-destructive and minimally destructive methods applied to real case studies and treatments.