Objective: To evaluate the immune function of epitope peptides interacting with porcine PD-1 or PD-L1. Methods: We optimized and synthesized peptides (PD-L14QN-GF and PD-L14QN-AF) using the solid-phase method and assessed their effects on peripheral blood mononuclear cell (PBMC) proliferation and PD-1 and cytokine expression after porcine reproductive and respiratory syndrome virus (PRRSV) infection in vitro and on antibody responses to a porcine circovirus type 2 (PCV2) vaccine in vivo. Results: The optimized peptides PD-L14QN-GF and PD-L14QN-AF exhibited lower binding free energy and higher stability when interacting with the PD-1 target protein.Under both PRRSV-infected and non-infected conditions in vitro, both peptides enhanced the proliferation of PBMCs, inhibited PRRSV RNA replication, and downregulated PD-1 transcription levels. Additionally, PD-L14QN-GF and PD-L14QN-AF upregulated the mRNA transcription and protein secretion of interleukin (IL)-2, IL-10, and interferon-γ to varying degrees. In vivo experiments demonstrated that PD-L14QN-GF significantly increased the antibody titer and seroconversion rate of the PCV2 vaccine. Conclusions and Relevance: PD-L14QN-GF and PD-L14QN-AF induced stronger immune responses than PD-L14. PD-L14QN-GF has potential as an immune-enhancing adjuvant.