Cnidarian venoms are rising as a new source of potential pharmacologically active molecules. They have been investigated for their neurotoxins acting on several nervous system targets but little is known about their antimicrobial and antiparasitic properties. Giardiasis, a common disease in developing countries, is produced by the protozoan Giardia duodenalis which induces severe gastroenteritis when infecting humans. The aim of this study is to describe the structural and molecular effects of Linuche unguiculata jellyfish extract on G. duodenalis. In this study, the effects on the ultrastructure were observed by electron transmission microscopy 24 h after the exposure to the extract and to the commercial antiparasitic drugs metronidazole, nitazoxanide and albendazole. To assess the effect at the molecular level, the gene expression analysis of β-tubulin, β-giardin, cysteine protease and glutamate dehydrogenase of G. duodenalis exposed to Linuche’s extract was performed by the RT-PCR technique. Our results show that the exposure to venom caused severe changes on Giardia’s cellular organelles such as submembrane vesicles, nuclei and adhesive disk. Our experiments also showed that the extract significantly alters the expression of genes that encode for the structural protein β-tubulin and the enzyme glutamate dehydrogenase, which are related to cell viability.