Antimicrobial peptides are active against a diverse spectrum of microorganisms. Using a bioinformatics method, six potential novel antimicrobial peptides, A1, C1, A2, A3, C2 and A4, were identified in the C8α complement component. The corresponding genes were then cloned into a new vector as fusions with the self-cleavage protein Npro protein mutant EDDIE gene. The expressed or synthetic peptides, A1, A2, A3 and A4, showed antimicrobial activities against several bacteria, while peptides C1 and C2 did not. Peptides A1 to A4 showed no hemolytic activities over 3 h when at 500 μg/ml. Thus, A1, A2, A3 and A4, derived from the C8α complement system, are novel antimicrobial peptides.