Background: Metronidazole (MTZ) is the drug of choice for treatment of giardiasis, but it has many drawbacks and there is a need to find out medicinal plants having anti-giardiasis efficacy to be alternative to MTZ. Objectives: This work aimed to study the in vitro and in vivo anti -giardial effectiveness of the aqueous extracts of two plants; Cymbopogon(C.)citratus and Pulicaria (P.)undulata in comparison with MTZ. Methodology: For in vitro study, one mL from different concentrations of plant extracts and MTZ were added to one mL of Giardia cysts suspension for 5, 15, 30 and 60 min. The viability was distinguished by 0.1 % eosin. Also, morphological alterations of Giardia cysts were examined by scanning electron microscope (SEM). For in vivo study, 50 male Albino mice were divided into: Group I: non-infected control; Group II: infected-untreated (IU); Group III: infected-treated with 15 mg/kg of MTZ; Group IV: infected treated with 500 mg/kg of C. citratus extract and Group V: infected- treated with 200 mg/kg of P. undulata extract. The effectiveness of the extracts was evaluated by cyst count per gram of feces, histopathological and transmission electron microscopic (TEM) examination of the small intestine. Results: in vitro mortality percentages of Giardia cysts showed a significant dose and time dependent effect regarding each extract. The aqueous extract of C. citratus extract at 500 ug/mL revealed the highest significant mortality percentages. P.undulata at 400ug/mL, MTZ and C. citratus at 250 μg/mL showed high mortality percentages with significant differences on comparison with C. citratus at 500 μg/mL. The ultrastructure morphological alternations of G. lamblia cysts were observed mainly with C.citratus. In the in vivo study, C. citratus revealed significant early complete absence of the parasite from fecal samples at 5th days post treatment, while P. undulata and MTZ achieved complete cure at 10th days post treatment. Progressive improvement of intestinal mucosa pathological changes and the mucosal ultrastructure were observed in the treated mice. Conclusion: C.citratus and P. undulata aqueous extracts were effective against G. lamblia both in vitro and in vivo and they could be natural therapeutic alternative agents to MTZ.