Scaffolds form an integral part of tissue engineering applications. Amniotic membrane has been implicated in an extensive range of clinical usages. Although decellularized human amniotic membrane has been used in several tissue engineering applications, there is limited data on the biomechanical characteristics of amniotic membrane scaffolds for tissue engineering applications. The main goal of this study is to investigate various distinctive features of human amniotic membrane scaffold and present a comparative evaluation of this natural scaffold to synthetic (PLGA) as well hybrid hydrogel scaffolds, to gain a broader perspective on these scaffolds. In this study, we have fabricated synthetic PLGA, hybrid hydrogel scaffolds. Also, prepared decellularized human amniotic membrane then compared the mechanical, physical and biological characteristics of natural decellularized full-term amniotic membrane scaffold (AM), hybrid hydrogels consisting polyacrylamidealginate scaffold (HP) and synthetic PLGA scaffolds respectively (N = 3). The useful mechanical categorization data suggests AM and PLGA possessed better mechanical properties than HP hydrogels. The ultimate tensile strengths of AM and PLGA were comparable. The young’s modulus and stiffness of PLGA were relatively greater than AM. On the contrary, AM had a better modulus of toughness than PLGA. The study of physical properties indicated that AM exhibited lesser swelling compared to PLGA or HP. In term of elasticity, AM managed better elasticity than PLGA. However, the AM had lower elasticity compared to hybrid hydrogels. The density of AM was very less compared to synthetic PLGA or hybrid hydrogel scaffolds. Further, we observed the rate of biodegradation of AM was higher in comparison to the synthetic PLGA or hybrid hydrogel HP polymers. Taking account of the ease of availability, the range of applications and intrinsic distinguishing features of AM, it should be an ideal scaffold for regenerative medical applications. © 2016 American Scientific Publishers.