Compound semiconductor nanomaterials, such as telluride nanowires, nanorods, and nanoparticles, have many unique properties for wide range of potential applications. The interaction between organoids (a biological system) and telluride nanowires is a crucial research area for human health in terms of its safety concerns. In this study, we demonstrated a case study on Bi2Te3 nanowires. Through live/dead cell viability testing, bright-light image analysis, and surface area calculations, we showed that 50 μg/mL Bi2Te3 exerts minimum influence on shrinking crypts and disrupting lumen structure, which causes unhealthy growth. Within this optimal concentration, Bi2Te3 nanowires can stay as a stable and non-toxic material inside the intestine. Unlike the previous studies of the cytotoxicity of Telluride nanomaterials interacting with single type of cells, our research demonstrated the first study of the interactions of engineered Telluride nanomaterials with a real complex gastrointestinal tract system as our primary small intestinal crypts were directly isolated from mice and grew into a self-renewable system with various types of cells and different cell pathways, which has the capability to mimic a fully functional intestinal epithelium layer for a realistic study inside the gastrointestinal tract. Most importantly, we showed that Bi2Te3 nanowires, under infrared exposure, can act as a potential shield to stimulate cell viability and improve cell survivability.