The worldwide river and tidal hydrokinetic power potential is considerable. Harnessing such potential could allow the generation of a significant amount of sustainable electricity for local uses. To the present, most studies on hydrokinetic power have focused on large-scale commercial technology development, large tidal farms planning, and high-intensity resources assessment. Reduced attention was oriented towards investigating possibilities for small to medium-size hydrokinetic plants. However, given the characteristics of rivers and estuaries, in most cases, relevant hydrokinetic power exploitation possibilities exist regardless of the dimensions of the region considered. The planning of small to medium-size hydrokinetic plants for various aspects differs from larger developments. In the present work, a method for assessing the hydrokinetic resource is proposed and applied to the case study of the Douro waterway, which is characterized by moderate flow speeds and limited water depths. A high-resolution shallow-water numerical model is set up using ocean and river inflow boundary conditions. The flow velocities are estimated for the neap-spring period for different freshwater discharges. The spots presenting the highest annual hydrokinetic power average were identified, maximum flow speeds of about 1 m/s were found, and an annual mean power of 0.4 kW/m2 was estimated, indicating that prospects for hydrokinetic energy harvesting exist.