Implantation of biomedical devices is followed by immune response to the implant, as well as occasionally bacterial, yeast and/or fungal infections. In this context, new implant materials and coatings that deal with medical device-associated complications are required. Antibacterial and anti-inflammatory materials are also required for wound healing applications, especially in diabetic patients with chronic wounds. In this work, we present hyaluronic acid (HA) hydrogels with triple activity: antimicrobial, immunomodulatory and miRNA delivery agent. We demonstrate that polyarginine with a degree of polymerization of 30 (PAR30), which was previously shown to have a prolonged antibacterial activity, decreases inflammatory response of LPS-stimulated macrophages. In addition, PAR30 accelerated fibroblast migration in macrophage/fibroblast co-culture system, suggesting a positive effect on wound healing. Furthermore, PAR30 allowed to load miRNA into HA hydrogels, and then to deliver them into the cells. To our knowledge, this study is the first describing miRNA-loaded hydrogels with antibacterial effect and anti-inflammatory features. Such system can become a tool for the treatment of infected wounds, e.g. diabetic ulcers, as well as for foreign body response modulation. This article is protected by copyright. All rights reserved.