The diffusiophoresis of a pH-regulated, zwitterionic polyelectrolyte (PE) simulating entities such as DNAs, proteins, and synthetic polymeric particles in a solution containing multiple ionic species is modeled theoretically. The results of numerical simulation reveal that the diffusiophoretic behavior of the PE is influenced significantly by its physicochemical properties, the solution pH, the bulk salt concentration, and the types of ionic species. In particular, both the magnitude and the sign of the PE mobility are influenced appreciably by the bulk salt concentration and the types of ionic species. We show that the induced electric field coming from the applied concentration gradient is weakened by the movement of H+ and OH−. This phenomenon is more appreciable when pH is away from the isoelectric point of a PE. The results obtained provide valuable and necessary information for the design of diffusiophoresis devices.