The escalating trend of microbial resistance has become a pressing global concern, challenging the effectiveness of antimicrobial agents in treating infections. This study was aimed at evaluating the antimicrobial activity of the n-hexane, ethyl acetate, and methanol extracts of Securidaca longipedunculata against selected human pathogens. The antimicrobial screening against bacterial pathogens- (e.g., Methicillin-resistant staphylococcus aureus, Vancomycin-resistant Enterococci, Staphylococcus aureus, Staphylococcus feacalis, Escherichia coli, Salmonella typhimurium, Pseudomans fluorescens and Klebsiella pneumonieae) and fungal pathogens (which includes Candida albicans, Candida krusei, Aspergillus niger, Aspergillus fumigates, and Microsporum canis) was performed using agar well diffusion and broth dilution methods. The results demonstrated significant antimicrobial activity, with higher efficacy against S. aureus. Susceptibility test results showed that the extract inhibited the growth of all the test organisms (bacteria and fungi) with a mean zone of inhibition range of 18-29 mm, with the exception of VRE, S. typhimurium, P. fluorescens, C. krusei and M. canis in all the three extracts, while Hexane extract showed no inhibition against E. coli and A. niger. The standard drugs sparfloxacin and ciprofloxacin (500 µg/cm3) had zone of inhibition ranging from 28 - 40 mm. While the antifungal drugs fluconazole and fulcin exhibited zone of inhibition ranging from 27 mm to 34 mm. The Minimum inhibitory concentration (MIC) for the extracts ranges from 62.5 - 250µg/cm3, while the Minimum Bactericidal/Fungicidal Concentrations (MBC/MFC) range from 250 - 500 µg/cm3, respectively. The ethyl acetate extracts possessed higher antimicrobial activity among the three extracts tested against S. Aureus. The findings suggest that S. longipedunculata leaves hold promise as a natural source of antimicrobial agents, warranting further exploration for potential therapeutic applications.