This study proposes a strategy for enhancing the radiation resistance of glass/fibers by introducing phase interfaces. Through phase-separation techniques and high-temperature annealing treatments, we constructed nanoscale phase interfaces engineered in erbium-ytterbium co-doped high-phosphorus silica glass with a specific density, stability level, and homogeneous distribution. Using high-resolution transmission electron microscopy, nuclear magnetic resonance, and spectroscopic analyses, we tracked the evolution of the internal microstructure of the glasses at the atomic level. The findings confirmed that annealing effectively controlled the density of the phase interfaces formed. Under 1 kGy X-ray irradiation, glasses with effective phase interfaces exhibited significant improvements in radiation-induced attenuation and photoluminescence intensity compared to pristine glasses. This indicated that effective interfacial engineering considerably enhances the radiation resistance of glasses. Furthermore, online irradiation tests on the Er3+/Yb3+ co-doped silica fibers supported this result. Compared to pristine fiber, fibers annealed for 3 hrs and annealed for 20 hrs with different phase interfacial densities showed 45% and 73% lower RIA at 1080 nm, respectively.