Periplanetasin-2 is a 15-mer antimicrobial peptide (AMP), derived from the American cockroach Periplaneta americana. This novel AMP exhibits potent antibacterial effect against several pathogenic bacteria including Escherichia coli. Distinct from the targeting cell membrane, which is the general antibacterial mechanism of AMP, periplanetasin-2 exerts its antibacterial activity via apoptosis-like death, which is physiologically and mechanistically similar to eukaryotic apoptosis. E. coli cells treated with periplanetasin-2 showed features of apoptosis in a concentration-dependent manner, such as membrane depolarization, DNA fragmentation, caspase-like protein activation, and phosphatidylserine externalization. These physiological changes were attenuated by pretreatment with the reactive oxygen species (ROS) scavenger, which demonstrates that periplanetasin-2 induced apoptosis-like death in E. coli by generating ROS. In addition, periplantasin-2-induced apoptotic death was affected by SOS response components. In the absence of RecA, an essential protein for SOS response, apoptosis did not occur and the antibacterial activity of periplanetasin-2 was decreased. In contrast, deletion of the SOS gene dinF caused higher ROS accumulation and apoptotic features were detected. Collectively, these results indicate that the antibacterial mechanism of periplanetasin-2 is ROS-induced apoptosis-like death, which requires RecA for proceeding it, and the role of DinF is assumed to contribute to the ROS defense SOS response.