Chemical control of bacterial plant diseases in agriculture mostly relies on copper-based bactericides, which possess limited efficacy. In addition, copper-resistant strains often emerge after continuous application of these compounds. Host defense peptides have been suggested as potential candidates to tackle the antibiotic resistance crisis. However, these type of peptides present two major disadvantages: the ability of bacteria to develop resistance towards them and their high cost. Recently, the concept of Random Peptide Mixtures (RPMs) has been introduced with a modification of the conventional Fmoc-based solid-phase synthesis method. It was previously shown that RPMs of hydrophobic and cationic amino acids, such as LPhenylalanine-L/DLysine (FK and FdK) display strong antimicrobial activity. In the current study, we explored the potential of RPMs as crop protection agents in vivo and in planta. Our findings suggest that the RPMs possess strong antimicrobial activity towards plant pathogenic bacteria and have the potential to serve as novel crop protection agents.