The emergence of Mpox as a significant zoonotic viral threat presents new challenges in gastrointestinal endoscopy. This article outlines the risk of Mpox transmission during gastrointestinal endoscopy, particularly through respiratory droplets and contact with the mucosal surfaces. Gastrointestinal endoscopy may also facilitate transmission by fomites, as the Mpox virus can persist on medical instruments and surfaces for long periods. Nosocomial Mpox transmission is a significant concern in both endemic and non-endemic regions. This highlights the necessity for enhanced infection control measures in gastrointestinal endoscopy, including pre-endoscopic assessment, proper use of personal protective equipment, and rigorous post-procedural disinfection. Additionally, vaccination of healthcare workers frequently exposed to high-risk situations is emphasized. Ongoing surveillance and monitoring of healthcare workers are key components in minimizing the transmission risk. Although no direct cases of Mpox transmission via gastrointestinal endoscopy have been reported, these recommendations mitigate the potential risks associated with such procedures and necessitate strict adherence to infection control protocols. By adhering to these protocols and adapting to current practices, gastrointestinal endoscopy can be safely performed during the Mpox upsurge, ensuring the protection of both patients and healthcare workers.