Protein domains are structural modules with distinct three-dimensional structures and biological functions. They have been widely used as important tools for drug discovery, including molecular probes for biochemical analysis and biopharmaceuticals themselves. Chemical synthesis enables the preparation of protein domains with high purity and homogeneity, as well as the modification with non-natural components. Especially, mirror-image protein domains, prepared by chemical synthesis using d-amino acids, should provide promising opportunities for exploring bioactive ingredients from non-natural chemical space. This thesis describes synthetic studies on several mirror-image protein domains of therapeutic importance, and their applications to developing non-immunogenic potential biopharmaceuticals.