Recently, high residue of antibiotics in aquaculture products, which is a serious problem in aquaculture industry, has caused not only difficulties for export but also human health problems. In fact, many publications mentioned solutions for alleviating antibiotic content in disease treatment. Application of metal and metal oxides nanoparticles in bacterial treatment has been attracted abundant interests because of their distinctive properties in killing bacteria. For example, TiO2 nanoparticles exhibit photocatalytic property in water producing reactive radicals for killing bacteria. Silver nanoparticles can interact with bacterial membrane and molecular structure leading to dysfuction of bacteria. In this study, a drug delivery system combining doxycycline (an antibiotic), TiO2 and silver nanoparticles was prepared by multi-step procedure with the aim of improving bacterial treatment effectiveness. Morphology, size, zeta potential, compositions, doxycycline content of the nanoparticles were characterized by field emission scanning electron microscopy (FESEM), x-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS) and UV-visible spectrometer (UV-Vis) methods. The results showed that doxycycline loaded Ag decorated TiO2 nanoparticles have spherical shape with diameter in the range of 50–100 nm, zeta potential of −34 mV. In vitro tests on White-leg shrimp (Litopenaeus vannamei) infected Vibrio parahaemolyticus demonstrated the potential of nanoparticles in preventing and treating disease induced by Vibrio parahaemolyticus on white-leg shrimp.