Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, in which autoreactive T and B cells play important roles. Other lymphocytes such as NK cells and innate-like T cells appear to be involved as well. To name a few examples, CD56^brightNK cells were described as an immunoregulatory NK cell subset in MS while innate-like T cells in MS were described in brain lesions and with proinflammatory signatures. Autologous hematopoietic stem cell transplantation (aHSCT) is a procedure used to treat MS. This procedure includes hematopoietic stem/progenitor cell (HSPC) mobilization, then high-dose chemotherapy combined with anti-thymocyte globulin (ATG) and subsequent infusion of the patients own HSPCs to reconstitute a functional immune system. aHSCT inhibits MS disease activity very effectively and for long time, presumably due to elimination of autoreactive T cells. Here, we performed multidimensional flow cytometry experiments in peripheral blood lymphocytes of 27 MS patients before and after aHSCT to address its potential influence on NK and innate-like T cells. After aHSCT, the relative frequency and absolute numbers of CD56^brightNK cells rise above pre-aHSCT levels while all studied innate-like T cell populations decrease. Hence, our data support an enhanced immune regulation by CD56^brightNK cells and the efficient reduction of proinflammatory innate-like T cells by aHSCT in MS. These observations contribute to our current understanding of the immunological effects of aHSCT in MS.