With the increased usage of silver nanoparticles (AgNPs), the potential impacts of released AgNPs in the environment are increasingly concerned, especially to natural living organisms. Since the properties of AgNPs significantly depend on their sizes, this work aimed to compare the effects of 5-nm and 70‐nm AgNPs on toxicity and bioaccumulation in Hoplobatrachus rugulosus, the edible East Asian Bullfrog. The synthesized AgNPs were characterized by X‐ray diffraction and selected area electron diffraction analyses. Both 5‐nm and 70‐nm AgNPs caused mortality, reduced growth, induced abnormal development, generated cellular oxidative stress, and modulated cellular biomolecule pattern of frog embryos, but at different levels. The 5‐nm AgNPs caused harmful effects on the frog embryos more than 70-nm AgNPs, likely due to their small size to allow more accessibility into the cell. The mortality effects of AgNPs depended on the concentration, exposure time, and size. The malformation of frog embryos in response to AgNPs-exposure included scoliosis, lordosis, kyphosis, and yolk sac edema. Synchrotron Fourier transformed infrared analyses revealed that 5‐nm AgNPs significantly changed the profile of cellular biomolecules in the embryos, indicated by the spectral peaks assigned to lipid, carbohydrates, proteins, and nucleic acids. The bioaccumulation of silvers was dominant in eggs, followed by stomach, liver, kidney, and intestine, respectively, suggesting their translocation via blood circulation. The result of high accumulated silver in eggs and effects on embryonic mortality, growth, development, and cellular changes suggested the potential negative impacts of AgNPs on the sustainability of this frog in the environment.