Cases of Monkeypox virus infection (Mpox) were initially relegated to Central and West Africa; however, in May 2022, outbreaks began to occur in non-endemic areas. Patients with Mpox infection can present with several symptoms in the gastrointestinal tract, such as abdominal pain, proctitis, and hematochezia. While several case reports have been published that show the presentation and management of patients with M. pox, it is fundamentally essential to have a collective resource for gastroenterologists to identify patients with this infection and appropriately manage them to ensure a safe outcome. The purpose of this book chapter is to present the variety of gastrointestinal manifestations that can present in patients infected with Mpox and the best way to manage them appropriately. We will present the current state of knowledge about gastrointestinal manifestations of Mpox by analyzing key studies that have been published to date and provide a broad overview of the subject as it pertains to gastroenterologists.