The synthetic epinecidin-122–42 peptide was derived from positions 22–42 of Epinephelus coioides epinecidin-1. The synthetic SALF55–76 cyclic peptide (csSALF55–76) and SALF55–76 linear peptide (lsSALF55–76) contained sequences from positions 55 to 76 of the Penaeus monodon anti-lipopolysaccharide factor (ALF), respectively. We studied the in vitro activities of epinecidin-122–42, csSALF55–76, and lsSALF55–76 against Propionibacterium acnes, Candida albicans, and Trichomonas vaginalis. The minimum inhibitory concentrations (MICs) of epinecidin-122–42 for the test pathogen strains ranged 12.5–200 μg/ml, those of csSALF55–76 ranged 100–200 μg/ml, and those of lsSALF55–76 ranged 25–200 μg/ml. epinecidin-122–42 exhibited cytotoxicity towards P. acnes, C. albicans, and T. vaginalis (one strain of which was a metronidazole-resistant strain, while the other strain was not), suggesting that epinecidin-1 functions like a lytic peptide. Similar cytotoxicity was identified against T. vaginalis treated with the csSALF55–76 and lsSALF55–76 peptides. The antimicrobial activities of these peptides were confirmed by scanning electron microscopy (SEM), transmission electron microscopy (TEM), a viable cell count assay, and flow cytometric analysis. TEM and SEM examinations of T. vaginalis treated with these three peptides showed that severe swelling preceded cell death and breakage of the outer membrane, and the intracellular inclusion was found to have effluxed extracellularly. This phenomenon was also found with epinecidin-122–42 treatment of P. acnes and C. albicans. Our results suggest that the epinecidin-122–42, csSALF55–76, and lsSALF55–76 peptides may be good candidates for treating trichomoniasis, and epinecidin-122–42 may have potential as a drug supporting therapy for acne and candidiasis.