A comprehensive model has been developed for calculating self-diffusion coefficients in mixed-solvent electrolyte solutions. The model includes methods for calculating the self-diffusion coefficients of ions and neutral species at infinite dilution and for predicting the effect of finite concentrations of electrolytes. For limiting diffusivities, a mixing rule has been developed for predicting the diffusivity in multicomponent mixed solvents using the limiting diffusivities or ion conductivities in pure solvents. The effect of finite concentrations of electrolytes is modeled by combining the contributions of long-range (Coulombic) and short-range interactions. The long-range interaction contribution is obtained from the mean spherical approximation theory of the relaxation effect, while the short-range interactions are represented using the hard-sphere model of diffusion. Aqueous species are characterized by effective species diameters, which are defined to reflect the interactions between the components of the solution. The model has been integrated with a thermodynamic speciation model, which makes it possible to take into account the effects of complexation or other reactions in the solution. The model accurately reproduces experimental self-diffusion coefficients of ions and neutral molecules in mixed solvents over wide ranges of concentrations.