Axial spondyloarthritis (AxSpA) is a chronic, inflammatory, autoimmune disease that predominantly affects the joints of the spine, causes chronic pain, and, in advanced stages, may result in spinal fusion. Recent developments in understanding the immunomodulatory and tissue-differentiating properties of mesenchymal stem cell (MSC) therapy have raised the possibility of applying such treatment to AxSpA. The therapeutic effectiveness of MSCs has been shown in numerous studies spanning a range of diseases. Several studies have been conducted examining acellular therapy based on MSC secretome. Extracellular vesicles (EVs) generated by MSCs have been proven to reproduce the impact of MSCs on target cells. These EVs are associated with immunological regulation, tissue remodeling, and cellular homeostasis. EVs’ biological effects rely on their cargo, with microRNAs (miRNAs) integrated into EVs playing a particularly important role in gene expression regulation. In this article, we will discuss the impact of MSCs and EVs generated by MSCs on target cells and how these may be used as unique treatment strategies for AxSpA.