Purpose of the work was to modified natural based eumelanin nanoparticles surface by dopamine self-polymerization (FEUNp), facilitating conjugation through polydopamine bioactive functional groups and improving nanoparticle surface hydrophilicity. SEM, TEM, and AFM characterization confirmed FEUNp spherical shape (230.04 ± 8.25 nm) and their polydopamine coating. Individual indole or indoline structure spectrum at 1600 cm^− 1 and C:N mass 9.08 was highlighted by FTIR and XPS analysis respectively. Quartz-crystal microbalance with dissipation monitoring (QCM-D) and thermal gravimetric analysis (TGA) showed successful polydopamine adsorption to eumelanin nanoparticles surface, a weight ratio of eumelanin nanoparticles/dopamine of 1/2.46 in the wet state and 1/0.20 in the dry state; the − 36.60 ± 0.45 mV negatively surface charges confirms the presence of PD covering. FEUNp were loaded with gentamicin sulfate, for application in infectious diseases therapies, such as osteomyelitis. Nanoparticles drug entrapment efficiency was 32.42 ± 3.21%, and ζ-potential close to neutrality (− 1.84 ± 0.58 mV). FEUNp-GS antimicrobial effect was tested on Staphylococcusaureus and Escherichiacoli showing gentamicin 24 h sustained release from FEUNp-GS. IC₅₀ and IC₉₀ were 110.60 μg/mL and 216.39 μg/mL against S. aureus, and 54.13 μg/mL and 101.25 μg/mL against E. coli. The results are promising for FEUNp-GS as delivery system potentially useful diverse administration routes.