Salt stress poses a significant threat to rice productivity and global food security. This study investigates the role of EBP1, a homolog of ErbB3 Binding Protein 1, in regulating salt tolerance in rice. We found that salt treatment induces OsEBP1 expression. Functional analyses reveal that overexpression of OsEBP1 enhances salt tolerance in rice, while knockout mutants show reduced salt tolerance. In the ebp1-1 mutant, salt stress leads to the downregulation of key ion homeostasis genes, including HKT1;1, SOS1, and HAK1, resulting in elevated Na+ levels and disrupted Na+/K⁺ balance. Additionally, OsEBP1 overexpression lines exhibit enhanced antioxidant defenses, characterized by reduced reactive oxygen species (ROS) accumulation and increased activity of antioxidant enzymes, such as APX, CAT, and POD. Further investigation reveals that EBP1 directly interacts with FKBP12, which promotes EBP1 degradation via the 26S proteasome pathway. Genetic analysis indicates that FKBP12 acts as a negative regulator of EBP1, and its downregulation stabilizes EBP1 levels under salt stress, thereby enhancing salt tolerance. In conclusion, these findings provide novel insights into the molecular mechanism underlying the FKBP12-EBP1 interaction in salt stress tolerance, providing a basis for developing salt-tolerant rice cultivars to bolster sustainable agriculture in salinity-affected regions.