Introduction: As the overuse of antibiotics increases, antimicrobial resistance is becoming a significant issue, making bacteria resistant to antibiotics and rendering illnesses more challenging to treat. The declining efficacy of synthetic antibiotics in curing infectious diseases is a global concern that is growing. Thus, studies for alternatives from natural plants are in high demand. Method: This study was done to assess the phytochemical compounds and antimicrobial activity of methanolic Muntingia calabura L. leaf methanolic extract against Staphylococcus aureus, Salmonella typhimurium, and Shigella sonnei using the disc diffusion and broth dilution methods. Results: The methanolic extract of M. calabura L. leaves was the most successful when tested against S. aureus with a mean inhibition zone of 14.33 mm, followed by S. sonnei with 10.66 mm, while no inhibitory effect was noted on S. typhimurium. When tested for minimal inhibitory concentration (MIC), readings of 7.81 mg/ml and 62.50 mg/ml were recorded for S. aureus and S. sonnei, respectively. The minimum bactericidal concentration (MBC) test revealed that the methanolic extract of M. calabura L. leaves completely inhibited S. aureus and S. sonnei at 15.63 mg/ml and 250.00 mg/ml, respectively. The effectiveness of M. calabura L. leaves in inhibiting the tested organisms demonstrates the extract’s potency as a remedy. Conclusion: The findings of this study offer a foundation for the potential use of M. calabura L. leaves in developing pharmaceuticals for a variety of illnesses caused by the microorganisms studied.