Isoprene-derived secondary organic aerosol (SOA) is mainly formed through acid-catalyzed reactive uptake of isoprene-derived epoxydiols (IEPOX) onto sulfate aerosol particles. The effect of IEPOX-derived SOA on the physicochemical properties of existing aerosols and resulting capacity for further SOA formation remains unclear. This study systematically examined the influences of IEPOX-derived SOA on the phase state, morphology, and acidity of pre-existing sulfate aerosol particles, as well as their implications on the reactivity and evolution of these particles. By combining aerosol thermodynamic and viscosity modeling, our predictions show that aerosol viscosity and acidity change drastically after IEPOX reactive uptake, with the aerosol becoming less acidic (increasing by up to 1.5 pH units) and more viscous by 7 orders of magnitude, thereby significantly reducing the diffusion time scale of the molecules inside the particles. Decreased aerosol acidity and increased viscosity co-contribute to a self-limiting effect where newly formed IEPOX-derived SOA inhibits additional multiphase chemical reactions of IEPOX. The relative contribution to the inhibitory effect of pH versus viscosity depends on the initial ratio of the IEPOX-to-inorganic sulfate aerosol, which differs between geographic regions. Moreover, reduced aerosol acidity and increased kinetic limitation to diffusion leading to lower hydronium ions and slower mixing times may impede other multiphase chemical processes after the formation of IEPOX-derived SOA. This study highlights important interconnections between physical and chemical properties of aerosol particles that come from interactions of inorganic and organic components, which jointly influence the evolution of atmospheric aerosols.