The global challenge of antibiotic resistance among gastrointestinal pathogens is increasing daily. Gastroenteritis is a major health challenge in developing countries and is ranked 8th among the top 10 causes of death in Namibia. While medicinal plants used in Namibia could be the source of medicine for gastroenteritis, there is a gap in knowledge regarding the efficacy and safety of most medicinal plants used in Namibia. The study aimed to evaluate the antibacterial and cytotoxicity of medicinal plants used in Namibia to manage gastroenteritis. Aqueous and methanol extracts were prepared from Lantana camara, Grewia tenax, Corchorus tridens, Albizia anthelmintic, and Terminalia sericea. Agar disc diffusion and resazurin-based microtiter dilution assay were used to determine the antibacterial activity. Antibiogram assay was used to determine the susceptibility of gastrointestinal pathogens to 11 clinically used antibiotics. Normal mouse embryo fibroblast cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay were used for the cytotoxicity test. A 70% multidrug resistance to ampicillin, cephalosporin, sulphamethoxazole, erythromycin, penicillin, vancomycin, and ampicillin was observed among clinical isolates of Salmonella and Escherichia coli. Meanwhile, L. camara methanol seed extracts showed potent antibacterial activity against clinical strains of E. coli and Salmonella spp. (20.67 ± 1.53 and 21.67 ± 0.58 mm, respectively), with MICs between 31.25 and 62.5 µg/mL. The IC50 of all extracts was ≥65.85.00 ± 0.58 µg/mL. The study showed that methanol extracts of L. camara, C. tridens, and T. sericea have potent antibacterial activity against multidrug-resistant clinical Salmonella and E. coli. Moreover, methanol extracts did not show significant toxicity to NIH/3T3 cells.