Background: The herbs have been used to prevent and treat many diseases, because of their safe and available. With unique properties of gold nanoparticles, and its accurate ability to deliver medicines, making it a suitable for chemotherapy. Objective: Citrullus colocynthis and gold nanoparticles were used in the treatment of Giardia lamblia in vitro, but not in vivo. Materials and methods: Experimental animals were divided into three groups, control non-treated group (sub divided into infected and non-infected), group B (treated and non-infected), and group C (infected and treated). All infected groups inoculated with 2 × 10 4 cysts and all treated groups received an aqueous extract of fruits and nanoparticles of C. colocynthis as well as gold nanoparticles Once as single and twice as combination therapy. Mean of cysts in the stool (from the third day of infection) and remaining trophozoites in the intestines (after the eighth day of treatment) were counted, compered the effect of single or combine agents use among infected (treated and non-treated) groups. Some hematological and chemical parameters in the non-infected (treated and non-treated) groups Were compared and the toxicity of that nanoparticles was estimated. Results: The current study revealed that combination therapy is better than a single treatment, and that treatment with gold plus C. colocynthis nanoparticles is better than treatment with gold nanoparticles and native C. colocynthis. The study did not record significant effect of all compounds in hematological and chemical parameters, although it recorded variations in the levels and concentrations of these parameters. Conclusion: Uses of C. colocynthis nanoparticles combined with gold nanoparticles has the Highest efficiency in Giardiasis treatment in vivo, but with an incomplete cure. Biological parameters may be considered in some safety when using this type of nanoparticle.