With the growing economy and technology, disease prevention and individual health are becoming more and more important. It is highly urgent to develop a non-toxic, self-powered, and safe high-voltage power source to prevent diseases spread by mosquitoes, especially in isolated or remote areas. Herein, we reported a high-performance rotary triboelectric nanogenerator (R-TENG) based on customized theoretical simulations and a ferroelectric nanocomposite intermediate layer. The customized theoretical simulations based on gradient electrode gaps were established to optimize gap angles and segment numbers of the electrodes, which could prevent air breakdown and enhance the R-TENG output energy by at least 1.5 times. Meanwhile, the electrical output performance of the TENG was further enhanced with a highly oriented BaTiO₃ (BTO) nanoparticles intermediate layer by about 2.5 times. The open-circuit voltage of R-TENG reached more than 6 kV and could continuously light 3420 light-emitting devices (LEDs) or 4 serially connected 36 W household fluorescent lamps. Therefore, a self-powered high-voltage disease prevention system is developed based on the high-performance R-TENG to reduce the risk of disease transmission. This work provides a prospective strategy for the further development of TENGs and expands practical applications of self-powered and high-voltage systems.