Renewable energy sources, due to their direct (e.g., wind turbines) or indirect (e.g., hydropower, with precipitation being the generator of runoff) dependence on climatic variables, are foreseen to be affected by climate change. In this research, two run-of-river small hydropower plants (SHPPs) located at different water districts in Greece are being calibrated and validated, in order to be simulated in terms of future power production under climate change conditions. In doing so, future river discharges derived by the forcing of a hydrology model, by three Regional Climate Models under two Representative Concentration Pathways, are used as inputs for the simulation of the SHPPs. The research concludes, by comparing the outputs of short-term (2031–2060) and long-term (2071–2100) future periods to a reference period (1971–2000), that in the case of a significant projected decrease in river discharges (~25–30%), a relevant important decrease in the simulated future power generation is foreseen (~20–25%). On the other hand, in the decline projections of smaller discharges (up to ~15%) the generated energy depends on the intermonthly variations of the river runoff, establishing that runoff decreases in the wet months of the year have much lower impact on the produced energy than those occurring in the dry months. The latter is attributed to the non-existence of reservoirs that control the operation of run-of-river SHPPs; nevertheless, these types of hydropower plants can partially remediate the energy losses, since they are taking advantage of low flows for hydropower production. Hence, run-of-river SHPPs are designated as important hydro-resilience assets against the projected surface water availability decrease due to climate change.