Multi-drug-resistant bacteria (MDR) are the cause of different infections and diseases that have affected humanity for a long time, and have been an emerging global health problem that has led to increased morbidity and mortality. The growing emergence of MDR bacteria has underlined the need for development and discovery of new antibacterial compounds. In this context, a series of new paeonol 1,2,3-triazole and ether derivatives were synthesized using copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction and nucleophilic substitution. Paeonol has been a natural product widely studied due to its many biological activities, as well as its derivatives. Three ether derivatives (two unpublished) and ten triazole derivatives (six unpublished) of paeonol were obtained, which were determined by nuclear magnetic resonance (NMR), Fourier transform infrared spectrometry (FTIR), Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and six of them by X-rays, which is the first study of this type presented for these compounds. All the synthesized compounds were evaluated as antibacterial agents against Staphylococcus aureus and Escherichia coli, obtaining a minimum inhibitory concentration (MIC) above 100 µg mL-1. The results showed that CuAAC and nucleophilic substitution were very useful to obtain new paeonol triazole and ether derivatives and the products were obtained in yields from 21.3 to 98.5%. The advantages of these reactions (high yield in most compounds, reaction time, low impurities) show that using the method to produce new derivatives is advisable thus assisting in the discovery of new potential bioactive compounds. Multidrugresistant Multi drug resistant (MDR time mortality context 1,2,3triazole 123triazole 1,2,3 1 2 3 copperIcatalyzed copper I catalyzed azidealkyne azide alkyne (CuAAC activities two unpublished NMR, NMR , (NMR) FTIR, FTIR (FTIR) Fouriertransform FTICR FT ICR MS Xrays, Xrays X rays, rays X-rays coli MIC (MIC 10 mL1. mL1 mL 1. mL-1 213 21 21. 985 98 5 98.5% high impurities 3triazole 123 1,2, (NMR (FTIR mL- 9 98.5 12 1,2 98. 1,