In large-dimensional wireless systems, such as cooperative multicell processing, millimeterwave, and massive multiple input multiple output systems, or cells having a high user density, such as airports, train stations, and metropolitan areas, sufficiently accurate estimation of all the channel gains is required for performing coherent detection. Therefore, they may impose an excessive complexity. As an attractive design alternative, differential modulation relying on noncoherent detection may be invoked for eliminating the requirement for channel estimation at the base station, although at the cost of some performance degradation. In this treatise, we propose low-complexity hard-input hard-output, hard-input softoutput, as well as soft-input soft-output quantum-assisted multiple symbol differential detectors (MSDDs) that perform equivalently to the optimal, but highly complex maximum a posteriori probability MSDDs in multiuser systems, where the users are separated both in the frequency domain and in the time domain. When using an MSDD, the detection of a user’s symbols is performed over windows of differentially modulated symbols; hence, they exhibit an increased complexity with respect to the conventional differential detector while simultaneously improving the performance of the system, especially at high Doppler frequencies.