Burn injuries without the normal skin barrier usually cause skin wound infections, and wound dressings are necessary. Although various dressings with antibacterial ability have already been developed, the biosafety and administration mode are still bottleneck problems for further application. Herein, we designed skin-like wound dressings based on silk fibroin (SF), which are modified with the gelatinase-cleavable self-assembled/antibacterial peptide (GPLK) and epidermal growth factor (EGF). When a skin wound is infected, the gelatinase over-secreted by bacteria can cut the GPLK peptides, leading to the in situ self-assembly of peptides and the resultant high-efficiency sterilization. Compared with the commercial antibacterial dressing, the SF-GPLK displayed a faster wound healing rate. When a skin wound is not infected, the GPLK peptides remain in the SF, realizing good biosafety. Generally, the EGF can be released to promote wound healing and skin regeneration in both cases. Therefore, skin-like SF-GPLK wound dressings with on-demand release of antibacterial peptides provide a smart administration mode for clinical wound management and skin regeneration.