5-Hydroxymethylfurfural (HMF) is a biomass-based chemical platform that can undergo many feasible reactions. One of the most important reactions is the oxidation to 2,5-furandicarboxylic acid (FDCA), which is the monomer for bioplastic production. In this work, the radiation method was used to investigate the conversion of HMF in both aqueous (DI) and dimethyl sulfoxide (DMSO) solutions. The effects of media solvents, atmospheric gases, HMF concentrations, additive bases, and absorbed doses of gamma radiation were studied. The results showed that the media solvent played a crucial role in HMF conversion under gamma irradiation. At 30 kGy, the HMF conversions in DI and DMSO were 92.1 and 24.1%, respectively, and the oxidation products were only found in the irradiated samples under DMSO. The HMF conversion and oxidation product formation increased with the gamma radiation dose. Moreover, it was found that FDCA stability toward gamma irradiation is highly sensitive in aqueous solution but relatively stable in DMSO. The results implied the alternative promising choice of radiation method compared with traditional methods. To join the bridge, the use of a mixture solvent DI/DMSO seems considerable in the future.