The reversible modification of proteins with lipoic acid (LPA)-derived polydisulfides (PDS) is an important approach toward the transient regulation and on-demand recovery of protein functions. The in situ growth of PDS from the cysteine (Cys) residue of a protein, however, has been challenging due to the near-equilibrium thermodynamics of the ring-opening polymerization of LPA. Here, we report the protein-mediated, aggregation-induced polymerization (AIP) of amphiphilic LPA-derived monomers at room temperature, which can be performed at a concentration as low as ∼2% of the equilibrium monomer concentration normally needed. The aggregation of monomers increases the effective monomer concentration in aqueous solutions to the degree that the polymerizations behave similarly to those in bulk. The PDS conjugation enhances the thermostability, protease resistance, and tolerance to freeze-thaw treatments of the target proteins. Moreover, the PDS conjugation allows rapid and convenient purification of Cys-bearing proteins by taking advantage of the liquid-liquid phase separation of the protein-PDS conjugates and the full recovery of native proteins under mild reducing conditions. This AIP effect may shed light on facilitating other polymerizations with a similar near-equilibrium character. The PDS conjugation can open up new avenues to protein delivery, dynamic and reversible protein engineering, enzyme preservation, and recycling.