Exploring the potential of natural bioactive peptides is becoming more and more important for new drug discovery. First isolated from the European wasp Vespa crabro, the antimicrobial peptide Mastoparan C was found in higher content than many other molecules in the Mastoparan family. In addition to the mast cell degranulation that is similar to some components in insect venom, this compound possesses remarkable biological activities such as broad-spectrum antibacterial and antifungal, inhibiting the proliferation of many human cancer cell lines. However, unfortunately, Mastoparan C has the notable side effect of causing mammalian hemolysis. By investigating its structure-activity relationships, this review pointed out some suggestions to overcome the disadvantages of this potential peptide and thereby support further in-depth study in the drug discovery field. Keywords: Mastoparan C, antimicrobial peptide, biological activity, structure-activity relationships.