The aim of this study was to assess the toxicity of Crotalaria bernieri, a medicinal plant native to Madagascar, on animals. From leaf powder previously treated with hexane, a methanolic extract (LME) was obtained in 20.59% yield. LME contained alkaloids, flavonoids, amino acids, tannins and polyphenols. Total alkaloids (TAE) were extracted from LME with a yield of 30.25%. The toxicity of the extracts was tested on warm-blooded animals (Mus musculus, Gallus gallus domesticus) and cold-blooded animals (Ptychadena mascareniensis, Cyprinus carpio and Xenopsylla cheopis). LME was toxic to mice by the oral, subcutaneous and intraperitoneal (i.p.) routes, but the i.p. (LD50 = 43.57 mg/kg) route was far more toxic than the other two. Five min LME’s injection by i.p. route, severe lesions were detected in the lungs, liver, and brain, characterized by vasodilatation and the presence of altered neutrophil polymorphonuclears. LME was also toxic to Ptychadena mascareniensis (LC50 = 52.59 µg/mL) and Cyprinus carpio (LC50 = 16.96 µg/mL). However, it was not toxic to Gallus gallus domesticus by oral and i.p. routes at a dose corresponding to the LD100 in mice. It was also not toxic to Xenopsylla cheops. TAE was far more toxic than LME, suggesting that the toxic principles could be alkaloidal in nature.