Site-selective protein modification strategies can be used to insert non-natural functional groups into protein structures. Herein, we report on the use of the bis-electrophile 3-bromo-2-bromomethyl-1-propene as a reagent to introduce an electrophilic handle at cysteine residues under mild conditions. This method is demonstrated on a variety of proteins containing a solvent-exposed cysteine residue, including an anti-HER2 nanobody. Chemically distinct protein conjugates are then efficiently formed through further reaction of the electrophilic site with various nucleophiles, including thiols and amines. The resulting chemically-defined conjugates are highly stable in the presence of glutathione or human plasma and retain both the structure and function of the native protein.