In arid and semi-arid parts of the world, river exploitation is intensive, involving water storage for irrigation or hydropower generation. In Greece, 100 small hydropower plants (SHPs) take advantage of less than 10% of the hydropower potential of low flow streams (<2 m3/s), a very small amount in relation to the 70% of the European Union. The energy policy of complete decarbonization of the country by 2023 on a national scale opens the road for new investments in SHP projects, especially in intermittent-flow streams of the Greek islands. Simulated flows by the Modello Idrologico SemiDistribuito in continuo (MISDc model) are used to construct the annual flow duration curve (FDC) to study and assess the hydropower potential of an intermittent stream (Tsiknias river, Lesvos, Greece). For Tsiknias River, but also for six other intermittent-flow rivers of Crete island, the capacity factor (CF), which represents the mean annual power of the hydropower plant, should remain >75% to exploit the river’s potential. The FDC and CF are essential in designing SHP projects in intermittent-flow streams with long no-flow periods. The development of public participatory approaches and a closer cooperation among policy makers and stakeholders should work to promote hydropower exploitation and accelerate licensing procedures.