Background: Giardia lamblia, a protozoan intestinal flagellate, is the causative agent of human giardiasis allover the world. The current therapeutic agents have considerable adverse effects or be contraindicated in certain clinical situations and may show failure due to drug resistance. Aim of the study: This study was to evaluate the in vivo therapeutic efficacy of Tomex versus Meteronidazole against giardiasis; to declare the histopathological changes of the intestinal mucosa, and their impact on the ultrastructure of the pathogenic trophozoites. Material and Methods: Fourty seven Swiss albino mice divided as following: Group I: 2 non-infected, non-treated mice. Group II: 15 mice, only infected (non-treated). Group III: 15 mice, infected with G. lamblia cysts and treated orally with Tomex. Group IV: 15 mice, infected with G. lamblia cysts and treated orally with Metronidazole. These mice were subjected to parasitological, histopathological and ultrastructural studies. Results: The patent period, intensity of infection, cyst shedding and cure rate in groups treated by Tomex revealed a highly significant difference in comparison with the non-treated control and insignificant difference in comparison with Metronidazole, a finding that might be beneficial in clinical situations, at least, where current chemotherapy is contraindicated. Conclusion: Tomex proved to be injurious to the parasite with evident morphological changes; causing improvement of histopathological changes of the intestinal mucosa, rapid clearance of the parasite and control of giardiasis.