Protozoa use iron to grow, feed, and cause harm through elaborate mechanisms to obtain it from the host. In addition, expression of virulence genes is affected by iron. In Entamoeba histolytica, the parasite that causes amoebic dysentery and complications in human organs, our group have previously reported the presence of an IRE/IRP-like (Iron Responsive Element/Iron Regulatory Protein) mechanism. Giardia duodenalis is another parasite of medical interest that causes giardiasis, including nutrient malabsorption syndrome and dysbiosis, among other complications, such as anemia in children with giardiasis. Moreover, expression of many putative giardial virulence factors by free-iron levels has been reported. Recently, we have reported stem-loop structures in some mRNAs coding virulence proteins from both parasites. However, much remains to be studied about the role of iron in pathogenesis. In this review, we summarize several aspects of gene expression regulation by iron in these protozoa as well as an iron regulatory mechanism in E. histolytica and discuss the possibility of an iron regulatory IRE/IRP-like mechanism in G. duodenalis.