Background: Coffee is one of the main sources of dietary melanoidins. Coffee melanoidins have antioxidant properties and are associated with protective effects against oxidative damage. The aim of this research was to study the potential of melanoidins obtained from coffee byproducts as functional ingredients to improve gastrointestinal health using normal human colon cells. Melanoidins were extracted from two coffee byproducts: coffee silverskin (CSE) and spent coffee grounds (SCG). Extraction was carried out by ultrafiltration using a 10 kDa molecular cut membrane. Safety of raw materials and isolated fractions was studied by microbiological analysis and determination of acrylamide, respectively. Characterization of coffee isolates was assessed by UV-Vis absorption spectroscopy, infrared spectroscopy, and determination of browning, protein content and antioxidant capacity measured by ABTS and formation of intracellular ROS in human intestinal cells (CCD18 cell line). The high molecular weight (HMW) enriched fraction showed antioxidant capacity and protected intestinal cells against induced oxidative stress. Coffee byproducts generated after the roasting process are a sustainable source of melanoidins that may act as antioxidants and therefore, may have the potential to be used as a functional novel ingredient for the prevention of gastrointestinal diseases caused by oxidative stress.Keywords: Coffee byproducts, gastrointestinal health, melanoidins, sustainable health.