Objective: This study aimed to demonstrate the potential immunomodulatory activity in mice of rice immunopeptide GBP1 （NSVFRALPVDVVANAYR） screened previously. Methods: Animal experiments were conducted to investigate the immunomodulatory mechanism of GBP1 peptide. RNA-Seq was used to sequence the transcriptome of mouse spleen tissues before and after GBP1 peptide treatment, and the molecular mechanism of GBP1 peptide immunomodulatory effect was explained. Results: In the GBP1 peptide treatment group, the number of spleen cells tended to be normal, the liver organ coefficient decreased significantly, and the serum IgG content was stable.GBP1 peptide can affect the expression of cytokines, mediate signal transduction pathways, and exercise immune regulation function, and inhibit the secretion of IL-2, IFN-γ and TNF-α in serum of mice. Through transcriptome analysis, 780 differentially expressed genes were obtained from spleen tissue, which were closely related to immune-related p53 signaling pathway, ferroptosis, complement and coagulation cascade in the body. Conclusion: GBP1 peptide can affect the expression of cytokines, mediate signal transduction pathways, and exercise immune regulation function.