Due to the abuse of antibiotics, drug resistance has become an urgent problem in public health and clinical practice. Recently, antimicrobial peptides (AMPs) have been considered as excellent antibacterial agents that are not inclined to induce the drug resistance of bacteria, but they are limited by their easy hydrolysis by enzymes and high cytotoxicity. In this work, we designed a strategy using amphipathic α-helical peptides coupled with antimicrobial peptides (AMPs) to fuse with liposomes to form functional antimicrobial liposomes (FALs) as typical bio-colloids. FALs can overcome the drug resistance of bacteria, improve antibacterial performance and biosafety, and prevent enzymolysis of the AMPs to enhance their stability. In detail, the pancreatic-enzyme-treated AMPs exhibited no antibacterial activity against E. coli and S. aureus due to the hydrolysis of peptide. In contrast, the FALs still maintained excellent antibacterial performance against both E. coli and S. aureus after being treated with pancreatic enzyme, and could be further applied in the treatment of skin wounds infected with S. aureus on mice. Hematoxylin (HE) staining and proliferating cell nuclear antigen (PCNA) were adopted for histological analysis, proving that the FALs constructed by such a strategy had broad application prospects in both wound disinfection and the promotion of wound healing.