AIMS: This study aims principally to explore the possible drug-drug interaction between Montelukast, a leukotriene receptor antagonist employed in asthma management, and Cefixime, a broad-spectrum cephalosporin antibiotic. The research aims to determine more especially how this interaction might affect the pharmacological efficacy of Cefixime, especially its antimicrobial action. Methods: Job’s plot analysis was used to evaluate the interaction by looking at the stoichiometry and complex formation between Cefixime and Montelukast. By measuring the zone of inhibition against bacterial strains, antimicrobial assays were also carried out to assess any alterations in the antimicrobial efficacy of Cefixime combined with Montelukast. Results: The plot analysis of the Job revealed a unique ^-shaped curve that pointed to a 1:1 complex formation between Cefixime and Montelukast, hence strong interaction. Cefixime alone had a 17 mm zone of inhibition in antimicrobial testing; when combined with Montelukast, this markedly decreased to 11 mm. This significant drop suggests that the interaction of Cefixime may be lessened antimicrobial power. Conclusion: The results imply that Cefixime and Montelukast have a major drug-drug interaction that probably leads to the development of a 1:1 molecular complex. This interaction changes Cefixime’s absorbance characteristics and significantly lowers its antimicrobial potency. These findings highlight the need of assessing such interactions to prevent suboptimal therapeutic results in patients taking both drugs.