The vibro-acoustic performance of a fluid-loaded periodic locally resonant (LR) plate was examined in this research, with a specific focus on the effect of water fluid on the vibration and sound radiation of the LR structure. The analytical models of the fluid-loaded LR plate’s band gap, vibration, and acoustic radiation were theoretically derived with closed-form solutions, which can be used to predict the general vibro-acoustic rules of underwater LR structure. The results show that the LR band-gap width and Bragg frequency are significantly reduced when water fluid is considered. Besides, the frequency range that can be tuned to control the vibration and sound radiation for the LR plate with fluid is much narrower than that without fluid. The reason for inducing the above effects was also given in this research, which can be physically explained by the attached mass caused by the water fluid. In addition, the reason for the enhanced radiation efficiency close above the band gap was also discussed, which is caused by the change of radiation mode from corner or edge radiation to monopole radiation. Furthermore, adding small damping into the resonator could reduce the vibration and sound radiation in the frequency range above or close below the band gap, inducing the attenuation zone to be significantly broadened. Thus, designing the periodic resonators with proper damping could be an efficient method to make the LR plate more beneficial for vibration and noise reduction in water-surrounding applications.