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The bacterial genus Vibrio is one of the ubiquitous bacteria found in coastal areas and waters. The strain Vibrio cholerae is recognized for its clinical, health, and economic impact. The spread of multidrug resistant clones is a threat to public health. The aim of this study was to search for Vibrio cholerae in water and then test the antibacterial effect of extracts of the medicinal plant Atriplex halimus on the isolates of Vibrio cholerae detected. Water samples from different sites in Mascara (Algeria) were taken. Vibrio cholerae strains were identified after isolation by biochemical testing and serotyping. Antibiotic resistance was determined by an antibiogram, and the antimicrobial potency of extracts of the medicinal plant Atriplex halimus was tested through agar diffusion and microdilution in liquid medium. The first results demonstrate the presence of Vibrio cholerae in the water sampled. These strains were multidrug-resistant to most antibiotics, particularly to ampicillin, tetracycline, amoxicillin, erythromycin, and doxycycline. The two plant extracts exhibit antibacterial activity against Vibrio cholerae. The aqueous extract has an inhibitory effect at concentrations of 100 to 200 μg/ml, while the methanolic extract is active at lower concentrations of 25 to 100 μg/ml. These results highlight the importance of identifying bioactive substances that can restore the effectiveness of various classes of synthetic antibiotics against these multidrug-resistant strains.