The recognized attrition of drug discovery has been the central motivation behind the work described in the following chapters. Such decline in the rate of discovery has been partially blamed on the exhaustive exploration of part of chemical space by largely flat, sp2-rich chemotypes, which, until recently, made up most screening libraries. The exploration of new chemical space through the incorporation of three-dimensional chemotypes has been adopted as a potential solution, which has proven effective as evidenced by the recent surge in three-dimensional molecular probes and therapeutics. All-hydrocarbon α-helical stapled peptides represent a class of such three-dimensional chemotypes that have proven capable of targeting the challenging intracellular protein-protein interactions (~80% of the proteome). Those cell-permeable mini-proteins have promoted peptide drug discovery to the main stage and the work described in this document is intended to buttress and exploit this rise to prominence. Because the chemical space of stapled peptides is relatively underexplored and due to the pressing need for new therapeutics in the face of global issues such as drug resistance, fast and deep exploration via the large numbers and diversity attainable in DNA-encoded chemistry is desirable. To do so, however, one needs a DNA-compatible synthetic toolkit to generate all-hydrocarbon staples on DNA-chemical conjugates and to perform peptide synthesis on DNA. Chapters 1 and 2 describe the development of such a toolkit. ii Chapter 3 finally discusses how the latter could be used for the exploration of the α-helical stapled peptide chemical space via DNA-encoded chemical libraries.