Background The majority of epidemic Vibrio cholerae strains have become resistant to multiple antimicrobial agents for many reasons, including mutations, horizontal gene transfers, etc. Therefore, secondary means of treatment are needed to overcome this impediment in combating cholera. Desmodium triflorum (L.) and Terminalia citrina (Roxb.) are extensively used in traditional medicine. Therefore, the present study aims to evaluate the antibacterial activity of methanolic and ethanolic extracts of Desmodium triflorum (L.) whole plant and Terminalia citrina (Roxb.) fruits against V. cholerae isolates. Methods Initially, different extracts of both plant materials were subjected to qualitative phytochemical screening. Anti-V. cholerae activities were assessed by performing MIC (minimum inhibitory concentration) test using disc diffusion method with different concentrations (1.25, 2.50, 8.00, 10.00, 12.50, 15.00 mg/ml) where standard discs of gentamycin and meropenem (10 μg/disc) were used. Further, Brine shrimp lethality bioassay was done to evaluate the extracts’ cytotoxic activities using different concentrations (800, 400, 200, 100, 50, 25, 12.5, 6.25 μg/ml) against vincristine sulphate. Results The preliminary screening confirms the presence of convenient phytochemical constituents like flavonoids, alkaloids, glycosides, tannins, etc., and are liable for the emergence of the antibacterial activities in different strains. The minimum inhibitory concentrations of both methanolic and ethanolic extracts of Terminalia citrina (fruits) and Desmodium triflorum (L.) (whole plant) were found to be 2.50 mg/ml and 5 mg/ml, respectively. Moreover, 100% mortality was observed only in ethanolic extract of Terminalia citrina fruits at the highest concentration (800 μg/ml). In comparison, the rest of the test extracts showed less than 90% mortality at the highest concentration (800 μg/ml). Conclusions Both plants possess significant phytoconstituents and showed appreciable anti-V. cholerae activities with mild toxicity. Hence, Desmodium triflorum (L.) whole plant and Terminalia citrina (Roxb.) fruits may be recommended as potential phytotherapy against cholera disease.