Purpose: In this study, for the first time, new nanoparticles of La 3+ /α-Al 2 O 3 were synthesized with the ultrasonic-assisted hydrothermal method in the presence of honey as an ecofriendly and natural reagent. Methods: The as-synthesized La 3+ /α-Al 2 O 3 nanoparticles were characterized using scanning electron microscopy (SEM), transition electron microscopy (TEM), X-ray diffraction spectroscopy (XRD), energy dispersive X-ray (EDX), UV-visible spectroscopy, and Fourier transform infrared spectroscopy (FTIR) techniques. In this work, we report optimum conditions to synthesize La 3+ /α-Al 2 O 3 nanoparticles as novel material and as a candidate for antibacterial activity in antibacterial drugs. Results and Conclusion: The XRD and SEM micrograph results demonstrate the formation of pure La 3+ /α-Al 2 O 3 nanoparticles with a particle size in the range of 30-80 nm. The synthesis parameters were systematically examined using analysis of variance (ANOVA) through 2k −1 factorial design, and the factors were an assay for product optimization. Various factors such as hydrothermal time, temperature, ultrasound irradiation and interaction between these factors were investigated on the product size of the products. To investigate antibacterial activity of the La 3+ /α-Al 2 O 3 nanoparticles with the minimum inhibitory concentration (MIC) method, different dilutions of nanoparticles as 64,32,16,8,4, 2, 1 and 0.5 μg/mL were dissolved in dimethyl sulfoxide and diluted using distilled water and added to the Mueller-Hinton agar medium containing Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa and Serratia marcescens as gram-negative bacteria and Bacillus subtilis, Staphylococcus aureus, S. epidermidis and Micrococcus luteus as gram-positive bacteria.