Background: The study was undertaken to determine the phytochemical screening and the antibacterial activities of Pistia stratiotes (water lettuce) against some clinically isolated fish pathogens. Methods: The healthy and disease free plants samples were collected from Jebba Upper Basin of River Niger and tested for their antibacterial activities and phytochemical properties. Pistia stratiotes aqueous extract was extracted using sterile distilled water. The Agar diffused methods were used to determine the antimicrobial actions of the plant against fish pathogens of Pseudomonas fluorescens, Escherichia coli, Salmonella typhi, Aeromonas hydrophila, and Vibrio anguillarum. Results: The antibacterial investigation of aqueous extracts revealed the significant activity against these bacterial. Moreover, phytochemical examination of the crude extract showed the occurrence of saponins, alkaloids, tannins, anthraquinones, flavonoids, and catechins, which completely inhibited the growth of V. anguillarum and E. coli. However, Salmonella typhi, Pseudomonas fluorescens, and Aeromonas hydrophila exhibited moderate varying levels of resistance. Conclusion: The finding of this study showed that bioactive resistance from Pistia stratiotes can help disrupt the activities of various fish bacterial in aquaculture practices