A study evaluated a UV-C LED water disinfection module using 270–280 nm GaN high-power chips, testing various configurations, structural parameters, and pressure conditions. At 9 L/min flow rate, dual-chip configurations (5-series-2-parallel, 4-series-2-parallel, 3-series-2-parallel) achieved irradiation intensities of 377, 320, and 273 µW/cm2, respectively, with a 99.999% Escherichia coli inactivation rate despite a 40% reduction in beads and 27.5% intensity drop. Structural optimizations included switching to a copper substrate (reducing optical power attenuation from 54 to 42%), increasing quartz tube diameter from 6 to 16 mm for longer UV exposure, and improving light utilization with high-reflectivity materials. Single-chip configurations (10, 8, 6 beads) yielded 305, 250, and 210 µW/cm2, respectively, 19%–23% lower than dual-chip setups, yet maintained 99.999% sterilization. The module, sealed with food-grade silicone, operated at 9 L/min under 0.12 MPa inlet pressure, with a maximum tolerance of 0.45 MPa, showing no leakage and high stability. These findings support the development of efficient, cost-effective UV-C LED water disinfection systems for practical applications.