The objective of this study was to evaluate the effectiveness of antibiotics and antimicrobial peptides against 10 strains of Xylella fastidiosa. The minimal inhibitory concentration (MIC) of 12 antibiotics and 18 antimicrobial peptides were determined by agar dilution tests and growth inhibition assays. Antibiotics with the lowest MIC for X. fastidiosa strains were gentamicin, tetracycline, ampicillin, kanamycin, and novobiocin, chloramphenicol, and rifampin. Plate growth inhibition assays showed that four of the antimicrobial peptides (Magainin 2, Indolicidin, PGQ, and Dermaseptin) were toxic to all X. fastidiosa strains. All X. fastidiosa strains were sensitive to several groups of antibiotics, and minor differences in sensitivity to several antimicrobial peptides were observed among strains. This study shows that antibiotics and antimicrobial peptides have some activity against the pathogen, X. fastidiosa and may have application in protecting plants from developing Pierce's disease.