In this study, the optimal combination concentration was first screened, and the potential targets of the combination of SA and BSA were further elucidated by detecting changes in antioxidant capacity and expression differences at protein levels. At the same time, in order to further investigate whether the combined effect of SA and BSA exerts a protective effect on boar sperm by activating the PI3K-AKT pathway, the level of core protein phosphorylation in the pathway was evaluated. Then by proteomic analysis find core proteins. The results showed that the sperm treated with 2 mg/ml SA and 5 mg/ml BSA showed the best motility parameters, the best functional integrity, and the strongest ability to alleviate oxidative stress. At the molecular level, we found that the S2-B5 group may regulate oxidative stress protein and pro-apoptotic protein activity through the PI3K-AKT pathway. It also indicates that the core differential proteins NME5 and GSTA2 have significant regulatory effects under the combined action of SA and BSA. However, further research is needed to elucidate the specific mechanism by which the combined treatment of SA and BSA attenuates oxidative stress through the interaction between PI3K-AKT pathway and NME5 and GSTA2.