Wound management poses a considerable economic burden on the global healthcare system, considering the impacts of wound infection, delayed healing and scar formation. To this end, multifunctional dressings based on hydrogels have been developed to stimulate skin healing. Herein, we describe the design, fabrication, and characterization of a sprayable hydrogel-based wound dressing loaded with cerium oxide nanoparticles (CeONs) and an antimicrobial peptide (AMP), for combined reactive oxygen species (ROS)-scavenging and antibacterial properties. We adopted a mussel-inspired strategy to chemically conjugate gelatin with dopamine motifs and prepared a hydrogel dressing with improved binding affinity to wet skin surfaces. Additionally, the release of AMP from the hydrogel demonstrated rapid release ablation and contact ablation against four representative bacterial strains, confirming the desired antimicrobial activities. Moreover, the CeONs-loaded hydrogel dressing exhibited favorable ROS-scavenging abilities. The biocompatibility of the multifunctional hydrogel dressing was further proven in vitro by culturing with HaCaT cells. Overall, the benefits of the developed hydrogel wound dressing, including sprayability, adhesiveness, antimicrobial activity, as well as ROS-scavenging and skin-remodeling ability, highlight its promissing translational potentials in wound management. Wound management poses a considerable economic burden on the global healthcare system, considering the impacts of wound infection, delayed healing and scar formation. To this end, multifunctional dressings based on hydrogels have been developed to stimulate skin healing. Herein, we describe the design, fabrication, and characterization of a sprayable hydrogel-based wound dressing loaded with cerium oxide nanoparticles (CeONs) and an antimicrobial peptide (AMP), for combined reactive oxygen species (ROS)-scavenging and antibacterial properties. We adopted a mussel-inspired strategy to chemically conjugate gelatin with dopamine motifs and prepared a hydrogel dressing with improved binding affinity to wet skin surfaces. Additionally, the release of AMP from the hydrogel demonstrated rapid release ablation and contact ablation against four representative bacterial strains, confirming the desired antimicrobial activities. Moreover, the CeONs-loaded hydrogel dressing exhibited favorable ROS-scavenging abilities. The biocompatibility of the multifunctional hydrogel dressing was further proven in vitro by culturing with HaCaT cells. Overall, the benefits of the developed hydrogel wound dressing, including sprayability, adhesiveness, antimicrobial activity, as well as ROS-scavenging and skin-remodeling ability, highlight its promissing translational potentials in wound management. Statement of Significance Various hydrogel-based wound-dressing materials have been developed to stimulate wound healing. However, from the clinical perspective, few of the current wound dressings meet all the intended multifunctional requirements of preventing infection, promoting rapid wound closure, and minimizing scar formation, while simultaneously offering the convenience of application. In the current study, we adopted a mussel-inspired strategy to functionalize the GelMA hydrogels with DOPA to fabricate GelMA-DOPA hydrogel which exhibited an enhanced binding affinity for wound surfaces, AMP HHC-36 and CeONs are further encapsulated into the GelMA-DOPA hydrogel to confer the hydrogel wound dressing with antimicrobial and ROS-scavenging abilities. The GelMA-DOPA-AMP-CeONs dressing offered the benefits of sprayability, adhesiveness, antimicrobial activity, as well as ROS-scavenging and skin-remodeling ability, which might address the therapeutic and economic burdens associated with chronic wound treatment and management. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. Various hydrogel-based wound-dressing materials have been developed to stimulate wound healing. However, from the clinical perspective, few of the current wound dressings meet all the intended multifunctional requirements of preventing infection, promoting rapid wound closure, and minimizing scar formation, while simultaneously offering the convenience of application. In the current study, we adopted a mussel-inspired strategy to functionalize the GelMA hydrogels with DOPA to fabricate GelMA-DOPA hydrogel which exhibited an enhanced binding affinity for wound surfaces, AMP HHC-36 and CeONs are further encapsulated into the GelMA-DOPA hydrogel to confer the hydrogel wound dressing with antimicrobial and ROS-scavenging abilities. The GelMA-DOPA-AMP-CeONs dressing offered the benefits of sprayability, adhesiveness, antimicrobial activity, as well as ROS-scavenging and skin-remodeling ability, which might address the therapeutic and economic burdens associated with chronic wound treatment and management.