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Aim: Multi-drug-resistant bacteria is a growing concern worldwide. Plants have emerged as a promising avenue due to their bioactive compounds. Newbouldia laevis and Stereospermum acuminatissimum are two plants with a long history of use in traditional medicine. This study aimed at exploring the antimicrobial activity of their extracts against multi-drug-resistant bacteria. Material and Methods: Extracts were prepared by maceration of pulverized leaves or stem barks (250 g) in 2L dichloromethane/methanol (30/70) filtered and the filtrate was dried using a rotary evaporator. The crude extracts were then tested against five pathogenic multi-resistant bacterial strains and Minimum Inhibition Concentration (MIC) was determined using the broth dilution method. The combinations of extracts and reference drug ceftriaxone was carried out following the checkerboard technique. Results: The overall results showed that Newbouldia laevis and Stereospermum acuminatissimum crude extracts contain various phytochemicals such as alkaloids, flavonoids, terpenoids, and polyphenols, which were found to be associated with strong anti-bacterial effects against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Klebsiella pneumonia, exhibiting MICs values ranging from 100 μg/ mL to 400 μg/mL. The combinatorial analysis showed a combination and strains dependent-out, including synergism, additivity, and antagonism. Conclusion: These findings suggest that Newbouldia laevis and Stereospermum acuminatissimum could be used as alternative sources of antimicrobial agents for treating bacterial infections [ABSTRACT FROM AUTHOR]