Protein/peptide synthesis and modifications have always been the cornerstone of modern biochemistry, chemical biology, biotechnology, and medicine. They open new avenues for studying the biological function of proteins with synthetic chemistry. With the inherent complexity of these macromolecules, the scientific community has consistently strived to establish methods to simplify the processes involved. The concept of "Simplicity for Complexity" in protein/peptide total synthesis and modification encapsulates this pursuit. It emphasizes the development of straightforward, efficient, and versatile approaches to handle the intricate structures and functions of proteins and peptides. These methodologies aim to simplify the traditionally complex process of protein/peptide synthesis, enabling more accessible and effective manipulation of these molecules for various applications, from drug development and therapeutic strategies to structural biology and protein engineering. In this presentation, I will discuss our recent works on the development of selective, operationally simple and powerful methods to manipulate peptides and proteins.