Collagen, an extracellular protein, covers the entire human body and has several important biological functions in normal physiology. Recently, collagen from non-human sources has attracted attention for therapeutic management and biomedical applications. In this regard, both land-based animals such as cow, pig, chicken, camel, and sheep, and marine-based resources such as fish, octopus, starfish, sea-cucumber, and jellyfish are widely used for collagen extraction. The extracted collagen is transformed into collagen peptides, hydrolysates, films, hydrogels, scaffolds, sponges and 3D matrix for food and biomedical applications. In addition, many strategic ideas are continuously emerging to develop innovative advanced collagen biomaterials. For this purpose, it is important to understand the fundamental perception of how collagen communicates with receptors of biological cells to trigger cell signaling pathways. Therefore, this review discloses the molecular interaction of collagen with cell receptor molecules to carry out cellular signaling in biological pathways. By understanding the actual mechanism, this review opens up several new concepts to carry out next level research in collagen biomaterials.