Giardia lamblia, protozoan intestinal flagellate, is the causative agent of human giardiasis. Currently used therapeutic agents have significant side effects or contraindicated in some clinical conditions and show failure due to drug resistance. This study evaluated the probiotic in vivo-therapeutic efficacy; potent Acidophillus probiotics versus metronidazole against giardiasis in experimentally infected mice, by histopathological changes of intestinal mucosa, and their impact on the ultrastructure of the pathogenic trophozoites. Forty seven Swiss albino mice were divided into groups: GI: 2 mice non-infected, nontreated mice. GII: 15 mice only infected with G. lamblia cysts, (non-treated). GIII: 15 mice infected and treated orally with potent Acidophillus probiotics. G IV: 15 mice infected with G. lamblia cysts and treated orally with metronidazole. All mice were subjected to parasitological, histo-pathological, goblet cells mucous secreting activity and trophozoite ultrastructural studies. There was high significant difference between the infected non-treated controls and potent Acidophillus-treated group concerning; patent period, infection intensity, reduction percentage of cyst shedding and cure rate, but without significant difference between potent Acidophillus-of treated group and metronidazole-treated group. Keywords: Giardia lamblia, Swiss albino mice, potent Acidophillus, Ultrastructure, Intestinal Mucus & Histopathology.