Various saponins have demonstrated allelochemical effects such as bactericidal impacts as well as antimycotic activity against some plant pathogenic fungi, thereby acting to benefit plant growth and development. A commercial saponin solution was evaluated for bactericidal effects against Escherichia coli and growth of lettuce (Lactuca sativa) in a hydroponic system. E. coli (P4, P13, and P68) inoculum at final concentration of 108 colony-forming units (cfu)/mL was added to 130 L of a fertilized solution recirculating in a nutrient film technique (NFT) system used to grow ‘Rex’ lettuce. After 5 weeks in the NFT system, E. coli populations were lowest in the inoculated treatment that did not contain any saponin addition (0.89 log cfu/mL) when compared with all other inoculated treatments (P < 0.001). The treatment containing 100 µg·mL−1 saponin extract had an E. coli population of 4.61 log cfu/mL after 5 weeks that was higher than treatments containing 25 µg·mL−1 or less (P < 0.0001). Thus, higher E. coli populations were observed at higher saponin concentrations. Plant growth was also inhibited by increasing saponin concentrations. Fresh and dry shoot weight were both higher in the inoculated and uninoculated treatments without the saponin addition after 5 weeks in the NFT system (P < 0.0001). Lettuce head diameter was smaller when exposed to saponin treatments with concentrations of 50 and 100 µg·mL−1 (P < 0.0001). Lettuce leaves were also tested for the potential of E. coli to travel systemically to the edible portions of the plant. No E. coli was found to travel in this manner. It was concluded that steroidal saponins extracted from mojave yucca (Yucca schidigera) are not an acceptable compound for use in mitigation of E. coli in hydroponic fertilizer solution due to its ineffectiveness as a bactericide and its negative impact on lettuce growth.