Pseudomonas aeruginosa like many pathogen bacteria produces various virulence factors and form biofilm that contribute to its pathogenicity and the growing resistance to antibiotics. The production of virulence factors in those multi-resistant bacteria is controlled by a mechanism of regulation termed quorum sensing. Interfering with this mechanism of bacterial communication constitute a strategy to attenuate bacterial pathogenicity. Our study aimed to assess the ability of Balanites aegyptiaca and Terminalia macroptera to interfere with the system of QS through inhibition of QS-controlled factors production and the formation of biofilm. Methanol extracts of galls, stem bark of B. aegyptiaca, and stem bark of T. macroptera were screened for anti-QS activity using Chromobacterium violaceum CV026 and P. aeruginosa PAO1. At a sub-inhibitory concentration of 100 µg/mL, galls and stem bark of B. aegyptiaca quenched the QS system by inhibiting violacein production on C. violaceum CV026 and pyocyanin production on P. aeruginosa PAO1. The bark of T. macroptera reduced significantly the production of violacein, pyocyanin and the formation of biofilm. Moreover, antioxidant activity of phenolic compounds contributes to reduce the oxidative stress induced by pyocyanin. Thus, T. macroptera is a potential candidate for the identification and isolation of news effective anti-QS compounds. This study introduces a possible validation for traditional use of B. aegyptiaca and T. macroptera and constitutes a new therapeutic approach for the treatment of infections caused by bacteria resistant to antibiotics.