A variety of drugs are used in giardiasis treatment with different levels of efficiency, presence of side effects, and even formation of resistant strains, so that it is important to search new only-one-dose treatments with high efficiency and less side effects. Kramecyne, an anti-inflammatory compound isolated from methanolic extract of Krameria cytisoides, does not present toxicity, even at doses of 5,000 mg/kg. The objective was to determine the antigiardial effect of kramecyne over Giardia intestinalis in vitro and in vivo and analyze the expression of genes ERK1, ERK2, and AK on kramecyne treated trophozoites by Real Time Polymerase Chain Reaction (RTPCR). The median lethal dose (LD50) was 40 μg/mL and no morphological changes were observed by staining with blue trypan and light microscopy; experimental gerbil infection was eliminated with 320 μg/Kg of weight. After treatment there were no differences between intestines from treated and untreated gerbils. Kramecyne did not have significant effect over ERK1 and AK, but there are differences in ERK2 expression (p = 0.04). Results show antigiardial activity of kramecyne; however the mode of action is still unclear and the evaluation of ultrastructural damage and expressed proteins is an alternative of study to understand the action mechanism.