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Abstract Protozoan diseases such as malaria, leishmaniasis, Chagas disease, and sleeping sickness still levy a heavy toll on human lives. Deplorably, only few classes of anti-protozoan drugs have thus far been developed. The problem is further compounded by their intrinsic toxicity, emergence of drug resistance, and the lack of licensed vaccines. Thus, there is a genuine exigency to develop novel anti-protozoan medications. Over the past years, melittin, the major constituent in the venom of European honeybee Apis mellifera, has gathered the attention of researchers due to its potential therapeutic applications. Insofar as we are aware, there has been no review pertinent to anti-protozoan properties of melittin. The present review outlines the current knowledge about anti-protozoan effects of melittin and its underlying mechanisms. The peptide has proven to be efficacious in killing different protozoan parasites such as Leishmania, Plasmodium, Toxoplasma, and Trypanosoma in vitro. Apart from direct membrane-disruptive activity, melittin is capable of destabilizing calcium homeostasis, reducing mitochondrial membrane potential, disorganizing kinetoplast DNA, instigating apoptotic cell death, and induction of autophagy in protozoan pathogens. Emerging evidence suggests that melittin is a promising candidate for future vaccine adjuvants. Transmission-blocking activity of melittin against vector-borne pathogens underscores its potential utility for both transgenic and paratransgenic manipulations. Nevertheless, future research should focus upon investigating anti-microbial activities of melittin, alone or in combination with the current anti-protozoan medications, against a far broader spectrum of protozoan parasites as well as pre-clinical testing of the peptide in animal models.