The multifunctional secondary metabolites known as cyclic lipopeptides (CLPs), which are produced by a large variety of bacteria, have become a key category of plant immunity elicitors. Pseudomonas-CLPs (Ps-CLPs) are extremely diverse in structure and biological activity. However, an understanding of CLP-plant structure-function interactions currently remains elusive. Here, we identify medpeptin, a novel CLP from Pseudomonas mediterranea that consists of 22 amino acids. Medpeptin is synthesized by a non-ribosomal peptide synthase (NRPS) gene cluster and regulated by a quorum-sensing system. Further research indicates that medpeptin does not exhibit antimicrobial activity; instead, it induces plant cell death immunity and confers resistance to bacterial infection. Comparative transcriptome analysis and virus-induced gene silencing (VIGS) reveal a set of immune signaling candidates involved in medpeptin perception. Silencing of a cell-wall leucine-rich repeat extensin protein (NbLRX3) or a receptor-like protein kinase (NbRLK25)—but not BAK1 or SGT1—compromises medpeptin-triggered cell death and resistance to pathogen infection in Nicotiana benthamiana. Our findings point to a noncanonical mechanism of CLP sensing and suggest perspectives for the development of plant disease resistance.