The tuned liquid damper (TLD) has been proven as an effective vibration mitigation device. However, it is less efficient and robust under seismic excitations. Addressing this issue, this study proposes a dual-mode-based design methodology utilizing a pair of isolated TLDs (ITLDs) for the multi-performance vibration mitigation of multi-degree-of-freedom (MDOF) structures. Oriented by the dual-mode control target, a series of 2DOF structures were considered, and a mechanical model of the considered ITLD was established. The modal analysis was performed for the primary structure, on the basis of which feasible installation methods for the ITLDs are proposed. Correspondingly, an extensive parametric analysis and a frequency response analysis were conducted, which revealed the control advantages of a pair of ITLDs, and we explored the potential optimal design for the liquid mass and added isolation layer. Inspired by the parametric analysis results, a mode-based design procedure is proposed for a pair of ITLDs by incorporating the modal characteristics of the primary structure. Finally, the ITLDs were applied in a multi-story building structure to illustrate the effectiveness of the devices and proposed design method. The obtained analysis results show that the dual-mode mitigation effect can be satisfactorily achieved using a pair of ITLDs with the proposed design approach, as well as synthetic functionality of the pair of ITLDs. The employment of a pair of ITLDs provided effective and robust mitigation of seismic responses for MDOF structures, yielding an improved multi-response reduction compared with the TLDs with the same parameters. In particular, the seismic-excited structural acceleration responses can be suppressed for different floors, which cannot be achieved by conventional TLDs.