This study looked into the chemical composition and antimicrobial properties of essential oil extracted from Aframomum melegueta seeds, commonly known as alligator pepper, using hydro-distillation method. GC-MS analysis showed that the oil contains terpenoids, along with significant phenolic compounds such as guaiacol, catechol, and isoeugenol, compounds known for their antimicrobial and antioxidant properties. Aframomum melegueta extract was screened for antimicrobial activity against some bacterial and fungal isolates using agar well diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal/fungicidal concentration (MBC/MFC) assays. Results indicated that the oil had a wide range of antibacterial activities, particularly against Klebsiella pneumoniae and Staphylococcus aureus, which were quite susceptible, whereas Pseudomonas sp. showed some resistance. Biological activity for fungi; Trichophyton rubrum and Aspergillus flavus were more sensitive than Aspergillus niger and Penicillium sp. However, most isolates revealed static effects instead of biocidal, at the concentrations tested. Although the extract was less active against resistant strains like Pseudomonas sp., it pointed to its possible potential as a rich bioactive compounds, a natural antimicrobial agent, a natural antioxidant and functional ingredient in foods, pharmaceuticals, and nutraceutical industries.