Ground substance is a term for the non-collagenous components of extracellular matrix. Cells are surrounded by extracellular matrix in tissues, which acts as a support for the cells. Ground substance traditionally does not include collagen but does include all the other proteinaceous components, including proteoglycans, matrix proteins and, most prevalent, water. The non-collagenous components of extracellular matrix will vary depending on the tissue where it is found.

Ground substance is amorphous, gel-like, and is primarily composed of glycosaminoglycans, proteoglycans, and glycoproteins.