Bacterial nanocellulose is a promising biomaterial extensively used in functional foods and for drug delivery. Moreover, its characteristics can further be potentialized whether coupled with natural bio-extracts to endow antibacterial activity. Persea americana or avocado seed extracts are rich in phytochemicals and have demonstrated their antioxidant, antimicrobial and enzymatic activities, therefore encapsulating them into bacterial nanocellulose (BNC) may offer a potential release system of antibacterial avocado seed compounds. Accordingly, this study explores the in-depth insight into the influence of different bacterial nanocellulose producing strains (Komagataeibacter hansenii and Komagataeibacter xylinus) and cultivation conditions (static and dynamic cultivation, fermentation time) on the bacterial nanocellulose productivity and characteristics. The obtained bacterial nanocellulose membranes and beads were characterized in terms of chemical structure, morphology and crystallinity. More profitable and productive K. xylinus was further selected for encapsulation (up to 72.89 mg) of avocado seed extracts into bacterial nanocellulose membranes and beads in order to comprehensively evaluate the kinetic release profiles and determine their antibacterial activity against Escherichia coli and Staphylococcus aureus. Results of the study show that the bacterial nanocellulose and avocado seed extracts biohybrids represent a promising immediate (up to 17.39 mg in 1 h) and sustained (up to 35.04 mg in 48 h) release systems. Kinetic release modeling and cytotoxicity assessments confirmed controlled release behavior and biocompatibility for safe antibacterial applications in cosmetics, functional foods and drug delivery.