This modelling study investigates potential effects of repeated loading and unloading of kilometres-thick ice-sheets on groundwater flow and radionuclide transport for a conceptual repository constructed 500 m below ground surface in a hypothetical sedimentary rock setting in Southern Ontario, Canada. Multiple modelling scenarios have been simulated to examine the sensitivity of model conceptualizations and key parameters. Results indicate that while repeated glacial cycles can boost radionuclide transport, the amount reaching the surface remains minimal owing to the extremely low permeability offered by the surrounding sedimentary rocks. No significant incremental adverse effects to humans and the environment are therefore anticipated as a result of these glacial cycles.