Cyclophosphamide (CP) impacts several types of normal and healthy tissues, especially reproductive organ. The current work sought to investigate the preventive role of the green tea ingredient epigallocatechin-3-gallate (EGCG) against CP-induced testicular damage in mice. Thirty mature male mice were randomly allocated to three groups (n=10). Group 1 functioned as the control. Group 2 was administered Mod with CP (50mg/kg/d) for five days. Group 3 received CP (50mg/kg/d) for 5 days and EGCG (80mg/kg/d) for the following 30 days. The findings demonstrated that EGCG enhanced testicular mass and indix. Evaluation of Histology and Transmission Electron microscopy analysis revealed that EGCG treatment mitigated CP-induced injury to testicular structures such spermatogonial cells and seminiferous tubules. A proteomics investigation of testis revealed that EGCG administration substantially affected the quantity of 863 proteins. GO and KEGG analysis revealed that these proteins were mostly found throughout development cell grouth and PI3K-Akt signaling pathway. The PPI network analysis and RT-PCR results showed that Cdk1, Kif11, and Aurka may be the targets for EGCG. This is the first study to indicate the preventive role of EGCG on CP-induced testicular damage, and EGCG might be a natural active ingredient for tolerance to the testis toxicity generated by CP.