Islet transplantation is considered the most promising treatment for type 1 diabetes. However, the clinicalsuccess is limited by islet dysfunction in long-term culture. In this study, we have utilized the rapid self-gelationand injectability offered by blending of mulberry silk (Bombyx mori) with non-mulberry (Antheraea assama) silk,resulting in a biomimetic hydrogel. Unlike the previously reported silk gelation techniques, the differences inamino acid sequences of the two silk varieties result in accelerated gelation without requiring any externalstimulus. Gelation study and rheological assessment depicts tuneable gelation as a function of protein concentration and blending ratio with minimum gelation time. In vitro biological results reveal that the blendedhydrogels provide an ideal 3D matrix for primary rat islets. Also, A. assama fibroin with inherent Arg-Gly-Asp(RGD) shows significant influence on islet viability, insulin secretion and endothelial cell maintenance.Furthermore, utility of these hydrogels demonstrate sustained release of Interleukin-4 (IL-4) and Dexamethasonewith effective M2 macrophage polarization while preserving islet physiology. The immuno-informed hydrogeldemonstrates local modulation of inflammatory responses in vivo. Altogether, the results exhibit promising attributes of injectable silk hydrogel and the utility of non-mulberry silk fibroin as an alternative biomaterial forislet encapsulation