The human body is a complex organism with self-regulating ability and can cope with external pressures and challenges. To protect the body from damage during exercise or confrontations, beneath the human epidermal layer, the human body has evolved a coverall gown: the extracellular matrix (ECM). ECM provides a suitable space for the survival and activity of cells in the body, and affects the behavior of cells through signal transduction system. Proteoglycans, particularly the small leucine rich proteoglycan (SLRP) family, have been shown to be molecules that play important roles in matrix remodeling and organ fibrosis, such as by affecting ECM components or altering the intracellular environment. But in recent years reports of SLRP families, their manifestations in different organs have not been consistent. Recent studies suggest that proteoglycans entering the blood in a soluble form hold promise as diagnostic biomarkers of organ fibrosis and may provide novel therapeutic strategies for fibrotic diseases. Herein, we discuss and review studies of SLRPs in multi-organ fibrotic diseases.