Antimicrobial resistance has become a great challenge in therapeutic medicine so much so that the World health organization forecasts the possibility of a post-antibiotic era where minor injuries may lead to mortality. Pseudomonas aeruginosa is among the list of organisms that are highly resistant to conventional antibiotics, partly due to its broad genome, which facilitates the elaboration of virulence determinants and rapid adaptation to various environments, in addition to its inherent resistance mechanisms. In view of this, alternative measures of controlling microbial virulence activities using novel approaches that do not disturb its growth and viability, also known as anti-virulence strategy, are gaining wider attention. Since plants are repositories of several metabolites with chemical defense system against environmental pathogens, through ethnobotanical led studies, the effect of Pistacia lentiscus fruit extracts originating from Algeria and forty plant extracts originating from North-Chile were biologically and chemically evaluated with the aim of deciphering their anti-virulence effects against P. aeruginosa. Furthermore, this study tried to gain more insight into the bioactive compounds and possible mechanism of action. From the results obtained, selected plant extracts attenuated P. aeruginosa mainly pyocyanin activity and /or elastase and rhamnolipids virulence production which appears to be associated with the inhibition of quorum sensing activities and the alteration in membrane activities. The anti-virulence effect of the selected extracts (P. lentiscus, Azorella atacamensis, Baccharis grisebachii, Haplopappus rigidus and Parastrephia terestiucula) were also validated in biological models of infections where they mediated the toxicity of P. aeruginosa towards A549 human monolayer cells and/or Caenorhabditis elegans nematode. Interestingly, growth of the pathogen was not affected. Further chemical profiling of P. Lentiscus, and A atacamensis extracts revealed the presence of gingkolic acid and azorellane/mulinane diterpenoids as the putative bioactive compounds. Future studies intend to explore these extracts and their derived compounds on the potentiation of antibiotic activity in a panel of clinical strains. In general, this study sets the pace for the possible use of these plant extracts as adjuvants in treatment of P. aeruginosa infections.