Nanocrystalline materials with a high density of grain boundaries have long been reported to alleviate radiation damage. However, a full mechanistic understanding of defect reduction, particularly the interaction mechanisms between grain boundaries and clustered defects during irradiation, remains an open question. Here we present atomistic simulations of prolonged radiation damage evolution in Cu bicrystals with increasing radiation dose. Our results reveal the atomic details of defect nucleation and migration, and the mechanisms for the annihilation of defect clusters during irradiation. Stacking fault tetrahedra formed due to radiation damage cascades show preferential migration to irradiated grain boundary. Interstitial-loaded grain boundaries are observed to be dynamically resilient, and persistently interact with the stacking fault tetrahedra, revealing a self-healing response to radiation damage. The results show a synergistic effect of grain boundaries on defect annihilation at small grain spacings of less than 6 nm, giving rise to a drastic decrease in the density of defect clusters. These findings, along with the mechanistic insights, present an integrated perspective on interface-mediated damage reduction in radiation-resistant nanomaterials. Display omitted