Human post-partum tissue mesenchymal stromal cells (hPPT-MSCs) are widely used in research to investigate their differentiation capabilities and therapeutic effects as potential agents in cell-based therapy. This is ascribed to the advantages offered by the use of MSCs isolated from hPPT over other MSC sources. A paradigm shift in related research is evident that focuses on the secretome of the human MSCs (hMSCs), as therapeutic effects of hMSCs are attributed more so to their secreted growth factors, cytokines and chemokines and to the extracellular vesicles (EVs), all of which are components of the hMSC secretome. Positive therapeutic effects of the hPPT-MSC secretome have been demonstrated in diseases related to skin, kidney, heart, nervous system, cartilage and bones, that have aided fast recovery by replacing damaged, non-functional tissues, via differentiating and regenerating cells. Although certain limitations such as short half -life of the secretome components and irregular secreting patterns exist in secretome therapy, these issues are successfully addressed with the use of cutting-edge technologies such as genome editing and recombinant cytokine treatment. If the current limitations can be successfully overcome, the hPPT-MSC secretome including its EVs may be developed into a cost-effective therapeutic agent amenable to be used against a wide range of diseases/disorders.