Peptides play a crucial role in regulating plant responses to stress conditions. Small secreted peptides (SSPs) are known to be involved in immune response and are found in all land plants. However, the evolution of stress peptide signaling remains poorly understood. Here, we compared the pathogen-induced transcriptomes of the moss Physcomitrium patens, Zea mays, Brassica napus, and Solanum tuberosum to gain insight into the role of established SSP families from vascular and non-vascular plants in immune response. We identified 50, 76, 135, and 309 known SSP genes, differentially expressed during infection, in P. patens, S. tuberosum, Z. mays, and B. napus, respectively. In addition, a novel family of bryophyte-specific PSY-like peptides that are differentially regulated under infection was identified. The similarity of SSPs across the examined plant species was validated through a comparative analysis of peptide motifs and predicted three-dimensional structures. However, despite the similar patterns of antimicrobial peptide expression, only the RALF peptide family was differentially regulated under infection in both vascular and non-vascular plants. We also found that EPFL peptides, which are involved in growth and development processes in angiosperms, were differentially regulated in P. patens in response to pathogen infection. Thus, our study showed the complex nature of SSP signaling and shed light on the regulation of SSPs in different plant lineages during infection.