The progress of biomaterials and tissue engineering has led to significant advances in wound healing, but the clinical therapy to regenerate perfect skin remains a great challenge. The implantation of biomaterial scaffolds to heal wounds inevitably leads to a host immune response. Many recent studies revealed that the immune system plays a significant role in both the healing process and the outcome. Immunomodulation or immuno-engineering has thus become a promising approach to develop pro-regenerative scaffolds for perfect skin regeneration. In this paper, we will review recent advancements in immunomodulating biomaterials in the field of skin repair and regeneration, and discuss strategies to modulate the immune response by tailoring the chemical, physical and biological properties of the biomaterials. Understanding the important role of immune responses and manipulating the inherent properties of biomaterials to regulate the immune reaction are approaches to overcome the current bottleneck of skin repair and regeneration.