Abstract: An orally administered antibiotic encapsulated in nanospheres, as well as its preparation method and application. The antibiotic encapsulated in the nanospheres includes an antibiotic and a degradable biocompatible polymer that encapsulates the antibiotic, wherein biocompatible polymer includes monosaccharide-modified poly (ethylene glycol)-poly(lactic-co-glycolic acid) (PEG-PLGA), which can significantly improves the damage caused by oral antibiotics to the intestinal microbiota, avoids destruction of the microbial community, thereby preventing chronic diseases associated with intestinal microbial imbalance, and a good biocompatibility and long-term safety.