The zebrafish Danio rerio appears to be as an alternative experimental model mainly used on toxicological evaluations since the 1990s. In this chapter, we illustrate using a histopathological study the evaluation of a complex phytopreparation with janaguba milk (TPJM, used in popular medicine), which was administrated in zebrafish by immersion in water. We determined (1) lethal concentration 50 (LC 50)-1188.54 μg/mL; (2) the behavioral changes; and (3) the acute administration of TPJM modifications (48 h) at concentrations 500, 750, 1000, and 1500 μg/mL, on the histopathological parameters of the gills, kidneys, and liver. Also the concentrations of 1000 and 1500 μg/mL caused significant damage to the gill tissue and produced a high rate of histological changes in the liver. The kidneys showed greater changes at concentrations of 750, 1000, and 1500 μg/mL. Based on the percentage of TPJM extracts that was only 1.85%, the LC 50 was calculated as 475 mg/kg; according to traditional indication, only 6 tablespoons/day is consumed; and it is possible to infer that only 0.5 g of active ingredient is ingested by an adult user per day, corresponding to a dose of 7.14 mg/kg, which is far from the toxic effects, demonstrating low toxicity of TPJM.