Aphids are among the most injuring taxa for agricultural plants and their management presents one of the greatest challenges in agronomical research. The success of aphids as agricultural pests rely, among other factors, on their symbiotic relationship with an oblig- atory bacterium, Buchnera aphidicola, that provide them with nutrients missing from their unique diet source, the plant phloem sap. While the compartimentalization of those sym- bionts within specialized cells, the bacteriocytes and their vertical transmission from mother to offspring have been extensively studied, very little is known about the molecular effec- tors involved in the regulation of this symbiosis. Bacteriocyte-specifc Cysteine-Rich (BCR) peptides, a class of proteins recently identified in the pea aphid Acyrthosiphon pisum, are expressed exclusively in bacteriocytes and appear like promising regulators of this symbiotic interaction. Here, using the seven A. pisum BCRs as a reference, we identified 76 new pu- tative BCR sequences in the aphid lineage. They show no significant similarity with other sequenced organisms, confirming initial hypotheses that proposed BCRs as orphan genes. Using phylogenetic analyses, we grouped aphid BCRs into four subfamilies that differ in size and cystein-motif. To gain further insight into the function of these peptides, we used chemical synthesis and folding, combined with NMR to study the 3D structure of BCR4, one of the shortest BCRs. We showed that it belongs to a yet unknown structural class of defensin-like proteins, which shows similarity to cysteine-rich proteins regulating nitrogen- fixing endosymbionts in leguminous plant. Consistent with this, antimicrobial assays showed that BCR4 has bactericidal effect against the free-living Escherichia coli, a close relative of B. aphidicola. Moreover, BCR4 displays an outstanding insecticidal activity against the pea aphid in terms of both mortality and growth rate. Taken together these results suggest that BCR peptides could play a crucial role in the pea aphid physiology, possibly by regulating its endosymbiont populations.