Bone extracellular matrix (ECM) is comprised of organic and mineral components. Proteins, which are the primary constituents in the body that regulate all our actions, comprise the organic part of ECM. Collagen, a crucial and potent protein present in the body, mostly exists in supporting and connective tissues. Type I collagen is extensively used in the field of medicine because of its formation into fibrils consisting of triple helical polypeptide chains, which contribute to its remarkable mechanical properties. COL-V regulates the process of fibril production. There is conjecture that non-collagenous proteins may have a substantial impact on the regulation of hydroxyapatite mineral production, as well as the differentiation and attachment of cells. However, they possess several drawbacks such as restricted accessibility, high water solubility, and a lack of thorough understanding regarding their mechanism of action. Recently, multiple researchers have focused on striding each of these proteins individually, investigating their distinct characteristics and functions. Understanding the characteristics and dynamics of these proteins and their interactions with each other is crucial for the development of bone implants. ECM proteins can be employed either in their complete form or fragmented into peptides with specific sequences that will trigger the required reaction. For instance, collagen is commonly found in a variety of physical forms such as composites, sponges, membranes, films, solutions, gels, fibers, particles, powder, and so on. ECM proteins can also be utilized to enhance the biocompatibility of implants. This chapter will focus on the collagenous and non-collagenous proteins of the bone extracellular matrix.