The numerous side effects of conventional antibiotics and increasing antibiotics resistance of some strains of bacteria such as Staphylococcus aureus and Escherichia coli which are commonly implicated in skin infection, surgical site infections, urinary tract infections (UTIs), neonatal meningitis, systemic infections and enteric infections in humans makes it is pertinent to source for alternative remedies. Aim: To assess the antimicrobial activity of honey and garlic on Staphylococcus aureus and Escherichia coli Methodology: Standard microbiological procedures were employed to isolate and identify the bacteria species. Antimicrobial activity was determined using the agar well diffusion method. Result: The S. aureus and E. coli were susceptible to the honey and garlic extracts. S. aureus was susceptible to garlic, honey and the mixture of both with zones of inhibition ranging from 6.9-17.2mm, 4.8- 12.9mm and 6.0-17.0mm respectively while those of E. coli ranged from 5.8-16.4mm, 5.0-11.8mm and 5.6-16.0 respectively. There was significant difference (p ≤ 0.05) in the antimicrobial activity of the garlic, honey and the mixture. Conclusion: This study therefore reveals that honey and garlic possess significant antimicrobial activity against the tested organisms with high antibacterial activity occurring at high concentrations. Honey and garlic can therefore, serve as substitute to antibiotics