Injectable thermo-responsive hydrogels have been studied for various biomedical applications including; drug delivery, cell encapsulation, and tissue repairing. There are various natural and synthetic polymers which exhibit homogenous injectable solution at ambient temperature and form a gel in human body temperature. Polysaccharide, polypeptide and other biological macromolecule based hydrogels have been getting immense attention in biomedical application due to their low immunogenicity, abundance in nature, high biocompatibility and biodegradability. This manuscript focuses on polysaccharide and polypeptide based thermo-sensitive hydrogels, and some synthetic polymers which forms in situ gel in response to temperature change from ambient to body temperature. The value of numerous reactive functional groups of biological macromolecular polymers has been discussed for effortless modification and design of bio-macromolecule based thermo-sensitive hydrogels. In addition, we emphasized on the basic mechanisms of the thermo-response processes, the strategies to optimize the desired properties and their applications in local delivery approach.