Protein therapeutics, including antibodies, play a clinical role in treating various diseases. However, the administration of these therapeutics can provoke immune responses, leading to the generation of anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs). Mirror-image peptides and proteins composed of d-amino acids offer an effective solution due to their resistance to proteolytic degradation in immune cells. Numerous examples of mirror-image peptides and proteins exist in the context of drug discovery. In this study, the author focuses on the mirror-image variable domains of the heavy chain antibodies (d-VHH) as a novel d-protein-based scaffold with high-affinity target binding and low immunogenicity. This thesis describes the synthetic methods and characteristics of d-VHHs as well as the development of a screening process from a mirror-image VHH library. Additionally, this thesis details the chemical synthesis of therapeutic targets for applications in screening of mirror-image molecules.