Introduction. As oral mesenchymal stromal cells (MSCs) have not, to date, been isolated from systemic sclerosis (SSc) patients, the aim of this in vitro experiment was to characterize gingival MSCs (SScgMSCs) and granulation tissue MSCs (SScgtMSCs) from SSc and to evaluate their functionality in comparison to healthy MSCs (hMSCs), in normal or hyaluronic acid (HA) culture media. Materials and Methods. Isolated cells were described by immunophenotyping of surface antigen make-up and by trilineage mesenchymal differentiation capacity. Colony-Forming Unit-Fibroblast (CFU-F) test and migration potential evaluated MSC functionality. Results. All types of MSCs displayed positivity for the following surface markers: CD29, CD73, CD90, CD105, CD44, and CD79a. These cells did not express CD34, CD45, HL-DR, and CD14. Isolated MSCs differentiated into osteoblasts, adipocytes, and chondroblasts. The frequency of CFU-F for SScgtMSCs was significantly lower than that of hMSCs (p = 0.05) and SScgMSCs (p = 0.004) in normal medium, and also markedly lower than that of SScgMSCs (p = 0.09) in HA medium. Following HA exposure, both SScgMSCs and SScgtMSCs migrated significantly less (p = 0.033 and p = 0.005, respectively) than hMSCs. Conclusions. A reduced functionality of MSCs derived from SSc as compared to hMSCs was observed. HA in culture medium appeared to significantly stimulate the migration potential of hMSCs.