Abstract: The present invention provides for silk fibroin-based compositions comprising one or more antibiotic agents for prevention or treatment of microbial contamination, methods of making antibiotic-containing silk scaffold, methods of stabilizing antibiotics in silk scaffolds, and methods for preventing or treating microbial contamination using the antibiotic-containing compositions. Various methods may be used to embed the antibiotic(s) into the silk fibroin-based compositions. The antibiotic-containing compositions of the invention are particular useful for stabilizing antibiotics, preventing bacterial infections, and for medical implants, tissue engineering, drug delivery systems, or other pharmaceutical or medical applications.