Milk has long been associated with good health and is one of the most consumed beverages throughout the world. Exosomes are 30-150 nm membranous vesicles of endocytic origin that are released by all cell types and are also detected in bodily fluids including milk. These extracellular vesicles play significant role in intracellular communication and immune modulation via transferring functionally active cargo (miRNA, mRNA and proteins). Whether these milk-derived exosomes can serve as cross-species messengers and have a biological effect on host organism has been poorly understood. Here, we examined the stability of bovine milk exosomes in harsh environmental conditions. It was concluded that milk-derived exosomes are remarkably stable in both acidic and high temperature conditions while colorectal cancer cell-derived exosomes were not. Next, we studied the biodistribution of bovine milk exosomes using mouse models and IVIS imaging after oral administration. The results suggested that orally administered milk-derived exosomes can survive the harsh intestinal environment and can be trafficked to various organs. Interestingly, after 24 h, the milk-derived exosomes reached multiple organs including liver and spleen in the mice. To understand the role of milk-exosomes in cancer progression, in vivo mouse models implanted with colorectal cancer were orally administered with milk-derived exosomes. Remarkably, exosomes isolated from both raw and commercial (grocery store) milk significantly reduced the tumor burden. Furthermore, orally administered milk-derived exosomes prolonged the survival of the mice by inhibition of tumor-induced weight loss in cancer cachexia mice models. Thus this study provides new insights on the significance of milk-derived exosomes in context of mammalian physiology as well as prompt their use as drug delivery vehicles in therapeutic interventions.