As acid-catalyzed processes are ubiquitous in enzyme active sites, numerous protein bioconjugation approaches have been also leveraged by a range of acid catalysts. In natural systems, enzymatic catalysis often depends on acid-mediated activation of weak electrophiles in proteins including proteolysis of amide backbones through interaction of acids to the carbonyl groups. While such enzymatic catalysis could often be substrate-specific processes, acid-catalyzed chemical modification of proteins can offer broader substrate scope with a potentially unique reactivity and selectivity paradigm. One of the traditional approaches for acid-catalyzed protein modification is to employ strong Brønsted or Lewis acid (e.g., zirconium (IV) chloride-derived acid and perchloric acid) to enable reactions of weak electrophiles such as amides and carboxylic acids, although such harsh conditions may not be compatible with many protein substrates. More recently, various chemical strategies (e.g., sophisticated ligand design, proximity-accelerated catalysis through reversible covalent bond formation, and nonaqueous systems) have been devised to overcome the challenges, as described in the following sections. It is noteworthy that the development of many of those acid-catalyzed protein bioconjugation methods has been driven by knowledge of synthetic organic chemistry including Lewis acid strengths, 163 metal affinity, and unique solvent properties. This section discuss catalysis by both Brønsted acid and Lewis acid including metal Lewis acid.