In this study, wastewater was analyzed for the presence of the antibiotics, tetracycline (Tet) and chloramphenicol (Chlor). Additionally, the antibiotic removal capacities of constructed wetland systems, with interacting macrophytes (Lemna gibba and Azolla filiculoides), substrates (sand and silt) and with or without microbial fuel cells (MFCs), were examined. To find the ideal wetland combination, a randomized 23 factorial design was applied, resulting in eight combinations in triplicate. The initial and final concentrations of antibiotics in the aquatic medium and in plants at the end of the experiment were measured with a high-performance liquid chromatography-diode array detector (HPLC-DAD) to verify the absorption rate. The results showed average Tet and Chlor concentration in wastewater samples 4.25 ± 3.95 and 1.87 ± 0.07 μg/L, respectively. All wetland types performed efficiently, removing a maximum of 100% tetracycline and chloramphenicol and a minimum of 99.45% and 97.84% Tet and Chlor, respectively. The average absorption of Tet and Chlor was 3.13 and 0.36 μg/g, respectively, in A. filiculoides; and the average absorption of Tet and Chlor was 2.08 and 0.08 μg/g, respectively, in Lemna. L. gibba had a higher biomass increase and a better relative growth rate than Azolla. In relation to electrical production, at first, all treatments were affected by the antibiotics; however, production increased as time progressed. Finally, the physicochemical parameters that improved with treatment were oxygen, oxidation-reduction potential and pH, whereas conductivity, dissolved solids, and salinity were most influenced by the silt substrate. Overall, although no wetland was ideal, all combinations were efficient at removing antibiotic contaminants.