Nano-sized radiosensitizers can be used to increase the effectiveness of radiation-based anticancer therapies. In this study, bimetallic, ~30 nm palladium-platinum nanoparticles (PdPt NPs) with different nanostructures (random nano-alloy NPs and ordered core-shell NPs) were prepared. Scanning transmission electron microscopy (STEM), selected area electron diffraction (SAED), energy-dispersive X-ray spectroscopy (EDS), zeta potential measurements, and nanoparticle tracking analysis (NTA) were used to provide the physicochemical characteristics of PdPt NPs. Then, PdPt NPs were added to the cultures of colon cancer cells and normal colon epithelium cells in individually established non-toxic concentrations and irradiated with the non-harmful dose of X-rays/protons. Cell viability before and after PdPt NPs-(non) assisted X-ray/proton irradiation was evaluated by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Flow cytometry was used to assess cell apoptosis. The results showed that PdPt NPs significantly enhanced the effect of irradiation on cancer cells. It was noticed that nano-alloy PdPt NPs possess better radiosensitizing properties compared to PtPd core-shell NPs, and the combined effect against cancer cells was c.a. 10% stronger for X-ray than for proton irradiation. Thus, the radio-enhancing features of differently structured PdPt NPs indicate their potential application for the improvement of the effectiveness of radiation-based anticancer therapies.