Antibodies have become a well-established tool in the fields of diagnostics and treatments, especially within oncology, immunology, and infectious diseases. Despite their effectiveness, antibodies are limited by their size, high production costs, and immunogenicity, which in the long run can lead to significant challenges in the medical field. Some well-researched options to antibodies are non-antibody proteins and peptide scaffolds. In this report, focus lies on providing an overview of designed ankyrin repeat proteins (DARPins), Ankyrons, Affibodies, Anticalins, Adnectins and bicyclic peptides, all different formats of non-antibody proteins and peptide scaffolds. Ranging from 1-20 kDa, these non-antibodies feature stable structural elements and modifiable regions for highly specific bonds with high affinity. While originating from natural sources, non-antibodies can be produced synthetically at a low cost, while also decreasing immunogenicity. This report presents the structures of the chosen six formats, and also their function in various applications, as well as their potential to overcome the hurdles of regular antibodies. With the increasing risks of emerging diseases and other health-related issues, non-antibody proteins and peptide scaffolds show great potential for replacing or assisting conventional antibodies in healthcare and biomedical research.