Medicinal plants have been playing a crucial role in drug discovery and development against infectious diseases. The antibacterial activity of methanolic crude extract of traditionally used Trichilia dregeana Sond. was evaluated against common bacterial pathogens. Agar well diffusion and broth dilution assays were used to evaluate the antimicrobial activity and minimum inhibitory concentration (MIC) of methanolic extract. The methanolic crude extract of Trichilia dregeana Sond. showed promising antibacterial activity against all tested bacterial isolates. A significant difference (p < 0.05) was observed in terms of susceptibility among Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa species isolates. A higher mean susceptibility or inhibition zone diameter to methanolic extract was observed in E. coli (19.6 ± 5.9 mm) and P. aeruginosa (18.4 ± 5.9 mm) compared to S. aureus isolates. Significant differences were also observed in the susceptibility of tested bacterial isolates at different concentrations of crude extract. A higher inhibition zone diameter was recorded in P. aeruginosa (27.2 ± 1.5 mm), followed by E. coli (25.2 ± 1.5 mm) and S. aureus (21.1 ± 1.4 mm) at a concentration of 100 mg/mL. A comparable inhibition zone of crude extract was observed with that of the positive control at a 100 mg/mL concentration against S. aureus and E. coli isolates. The findings indicated that bacterial growth inhibition increased as the concentration of the crude extract increased. All tested pathogenic bacterial species (Gram-positive and Gram-negative) were susceptible to plant leaf extract, even at lower levels of concentration. This showed the broad-spectrum activity of the plant extract against both Gram-positive and Gram-negative bacteria. The methanolic extract of plants is an effective antibacterial agent to treat bacterial infections since the extract showed significant antibacterial potency, comparable with that of the standard antibiotic disc. The findings are promising and encourage further investigation on the phytochemical, toxicological and pharmacological aspects of the crude extract to support their potential rational use in antimicrobial therapy.