Considering the growing hazards of ionizing radiation, developing new shielding glass systems is essential to increase radiation safety and diversity of material choices in the real-time monitoring field. Based on the excellent comprehensive performance exhibited by high-entropy oxide glasses (HEOGs) due to its unique component composition and high-entropy effect, B2O3-TeO2-BaO-Bi2O3-MO (W, Ta, Dy, Mo) HEOGs with heavy metal oxides as the fifth component were prepared via the melt-quenching process. Physical, structural, and optical properties analysis show that the tantalum pentoxide (Ta2O5)-optimized HEOG has higher densification, more continuous and compact network filling, and wider indirect optical bandgap (Eg) than other glasses. The radiation attenuation ability of HEOGs was evaluated utilizing the MCNPX simulation and Phy-X program. The minimum specific lead equivalent (PbE) value of all heavy metal HEOGs in the entire photon energy range (10-3-103 MeV) is much higher than all types of commercial lead glass in service, showing excellent comprehensive attenuation ability for X-rays, gamma-rays, and fast neutrons. In addition, the addition of Ta2O5 dramatically shortens the path and attenuation times required for incident photons to annihilate inside the material due to the density increase effect brought by the high atomic number and high density. In the 100 MeV nuclear radiation area and the 0.08 MeV medical X-ray application zone, only 10 cm and 0.3 cm thickness are needed to achieve saturated absorption of photons.