Marine sponge explorations at Gulf of Mannar (GoM), India in the past few years (2003)(2004)(2005)(2006)(2007)(2008)(2009)) revealed around forty sponge species that lead to various comprehensive studies on chemicobiological molecules including collagens and their applications. Basing on the preliminary evaluations on collagen content, four marine sponges Hyattella cribriformis, Fasciospongia cavernosa, Callyspongia fibrosa and Dysidea fragilis belong to the families Spongiidae, Thorectidae, Callyspongiidae and Dysideidae of the class Demospongiae, were chosen for macromolecular and micro-anatomical comparison. Microscopic examinations were performed to understand the form and arrangement of skeletal components in each sponge, where unique skeletal composition and spongin distribution is typical for all the sponges except D. fragilis, which is highly embedded with diversified oxeae. Biochemical analyses were performed to resolve the macromolecular content for each sponge species. Sponge D. fragilis was found to possess less protein content (57.26±3.36 mg/g freeze-dried sponge wt) when compared to other sponges and significantly, C. fibrosa possess high protein (209.55±9.53 mg/g) and other macromolecular contents, except pentose (24.12±1.21 mg/g). Different forms of collagens viz., Acid soluble (AS), salt soluble (SS) and insoluble (Ins) collagens are estimated to understand the variation in collagen make up in their respective tissues. The higher collagen content in C. fibrosa could propose to use this species as a potential model for targeting collagenous molecules towards human health benefits.