Hydrokinetic power generation is a relatively recent type of hydropower that generates electricity from kinetic energy of flowing water making the conversion process more competitive compared to traditional micro-hydropower. Few authors have already analyzed the use of standalone hydrokinetic systems for rural electrification, however, there is no available literatures investigating the possibility of using this technology in combination with other renewable energy sources or diesel generator. Therefore, the aim of this paper is to investigate the potential use of hydrokinetic-based hybrid systems for low cost and sustainable electrical energy supply to isolated load in rural South Africa where adequate water resource is available. Different hybrid system configurations are modeled and simulated using the Hybrid Optimization Model for Electric Renewable (HOMER) and the results are analyzed to select the best supply option based on the net present cost and the cost of energy produced. The simulation results from two different case studies show that hybrid systems with hydrokinetic modules incorporated in their architectures have lower net present costs as well as lower costs of energy compared to all other supply options where the hydrokinetic modules are not included.