Chemical functionalization of proteins has become an indispensable tool for chemical and biological studies. Recent effort has been focused on exerting a control of selectivity of the chemical reaction to connect a synthetic moiety onto a precise location of a target protein or onto a particular protein in a complicated mixture of a myriad of biomolecules. Such selective bioconjugation technologies have been increasingly studied within the past decade. This thesis focuses on development of site-specific/bioorthogonal modification of natural proteins by transition-metal catalysis without the aid of genetic incorporation of unnatural amino acids. The first two chapters review recent advances in technologies used at the interface between chemistry and biology. The first chapter covers novel site-specific conjugation technologies for antibodies mainly focusing on reports after 2014. The second chapter features application of dirhodium(II) complexes for a variety of applications such as potency enhancement as a metallodrug, identification of binding site as a transition-metal catalyst, and an indicator for decomposition of the metal complex. Development of novel selective protein modification technologies is discussed in chapter 3–5. With the rhodium(II)-metallopeptide catalysis developed in the Ball group, it is shown that site-specific modification of monoclonal antibodies are feasible through proximity-driven diazo decomposition reaction. Application of Chan-Lam cross coupling to bioconjugation method is described in chapter 4; copper(II)-catalyzed cross coupling with boronic acid reagents enabled amide backbone modification through directing effect of a neighboring histidine residue. Furthermore, unexpected reactivity of vinylboronate toward N-terminal amine group with ascorbate reagent is shown in the same chapter as well. In order for the abovementioned protein modification reactions, a facile and concise analytical technique is of great help. To that end, a new blot analysis is invented by performing click chemistry reaction on a blot membrane with luminogenic azide probes. Because of a lack of such a “turn-on” type luminescence azide probes, a series of luminogenic iridium (III) azide probes are designed, synthesized, and applied to biological experiments such as the blot membrane experiment and cellular labeling experiment.