Oral exposure is known as the primary way for silver nanoparticles (AgNPs), which are commonly used as food additives or antibacterial agents in commercial products, to enter the human body. Although the health risk of AgNPs has been a concern and extensively researched over the past few decades, there are still numerous knowledge gaps that need to be filled to disclose what AgNPs experience in the gastrointestinal tract (GIT) and how they cause oral toxicity. In order to gain more insight into the fate of AgNPs in the GIT, the main gastrointestinal transformation of AgNPs, including aggregation/disaggregation, oxidative dissolution, chlorination, sulfuration, and corona formation, is first described. Second, the intestinal absorption of AgNPs is presented to show how AgNPs interact with epithelial cells and cross the intestinal barrier. Then, more importantly, we make an overview of the mechanisms underlying the oral toxicity of AgNPs in light of recent advances as well as the factors affecting the nano-bio interactions in the GIT, which have rarely been thoroughly elaborated in published literature. At last, we emphatically discuss the issues that need to be addressed in the future to answer the question "How does oral exposure to AgNPs cause detrimental effects on the human body?".