Large-scale use of nitrofurans is associated with a number of risks related to a growing resistance to these compounds and the toxic effects following from their increasing presence in wastewater and the environment. The aim of the study was to investigate an impact of natural surfactant, saponins fromSapindus mukorossi, on antimicrobial properties of nitrofuran antibiotics. Measurements of bacterial metabolic activity indicated a synergistic bactericidal effect in samples with nitrofurantoin or furazolidone, to which saponins were added. Their addition led to more than 50% greater reduction in viable cells than in the samples without saponins. On the other hand, no toxic effect against human colon epithelial cell was observed. It was found that exposure to antibiotics and surfactants caused the cell membranes to be dominated by branched fatty acids. Moreover, the presence of saponins reduced the hydrophobicity of the cell surface making them almost completely hydrophilic. The results have confirmed a high affinity of saponins to the cells ofPseudomonasstrains. Their beneficial synergistic effect on the action of antibiotics from the nitrofuran group was also demonstrated. This result opens promising prospects for the use of saponins fromS. mukorossias an adjuvant to reduce the emission of antibiotics into the environment.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11274-023-03669-2.