In our search for new antiamoebic agents, a new series of ethyl and methyl quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives have been synthesized using the Beirut reaction. All compounds were characterized by spectroscopic techniques and elemental analysis. Antiamoebic activity was evaluated in vitro against Entamoeba histolytica strain HM1:IMSS by the microdilution method, and the structure-activity relationship was analyzed. We found that eleven quinoxaline derivatives showed greater activity than metronidazole and nitazoxanide with IC₅₀ values in the range 1.99-0.35 μM. Compounds T-001 and T-016 shows IC₅₀ values of 1.41 and 1.47 μM, respectively, with a value of selectivity index >60.