This study aimed to investigate the effects of radiotherapy on the mechanical, chemical, and surface properties of two recently introduced restorative dental materials (a glass hybrid and an alkasite), while two conventional restorative materials served as references. Material specimens of the experimental groups (irradiated) were compared to the specimens of the control groups that underwent the same preparation procedure but without irradiation. The experimental groups of restorative material specimens were irradiated with a total of 70 Gy over 35 days (2 Gy/day × 35 days), while the control groups received no treatment. The following properties were evaluated: surface microhardness (Vickers), surface roughness, color change, flexural strength, flexural modulus, material reliability, and infrared spectra. For the experimental groups, measurements were performed 24 h after specimen preparation, i.e., before radiotherapy and after the completion of the irradiation protocol. For the control groups, measurements were performed after the corresponding periods of no treatment. A statistically significant increase in microhardness (p = 0.001–0.004) and surface roughness (p = 0.013) was observed as a result of material aging/maturation in both the control and experimental groups. However, the only statistically significant difference between the control and experimental groups was observed in the discoloration of the conventional reference material (p < 0.001). In conclusion, no statistically significant negative effects of a therapeutic dose of radiotherapy on any of the tested properties of the alkasite and glass hybrid materials were observed, whereas only a minor negative effect of radiotherapy in terms of discoloration was found for a conventional resin composite that was used as a reference material.