Although natural antimicrobial peptides (AMPs) are endowed with excellent antimicrobial properties, only a few of them have been successfully translated to the market so far. This is mainly due to their short half-life, to their high susceptibility to protease degradation, and to the lack of appropriate strategies for their efficient targeted delivery. Hence, the development of an effective system to deliver AMPs to the site of infection is urgent. The system here selected is represented by bacterial cellulose nanoparticles (BCNPs). Nanocellulose has recently emerged as one of the most promising "green" materials, attracting great attention due to its unique features, including biodegradability, sustainability, biocompatibility, and special physicochemical properties. To produce BCNPs, Komagataeibacter xylinus has been selected as host producing strain. Once obtained BC macrofibers, the production of BCNPs was set up by enzymatic hydrolysis using a commercial mixture of cellulases from Trichoderma reesei to develop a sustainable green biotechnological process. The storage stability of produced BCNPs has been also evaluated. Obtained BCNPs have been functionalized through non-covalent bindings with an antimicrobial peptide previously identified in human apolipoprotein B and found to be endowed with strong antimicrobial properties in in vitro analyses and with good biocompatibility profiles when analyzed on human skin cells. This opens interesting perspectives to the applicability of the developed system in several biotechnological fields.