Foodborne illnesses are often caused by microbial contamination during preparation or storage. In this work, stable nanoemulsions of clindamycin were prepared using Mentha piperita essential oil (MEO) as a nanocarrier delivery system. Response Surface Methodology was used to optimize the key variables for clindamycin nanoemulsion formulation, including 4.83, 2.83, and 0.14%w/w surfactant, essential oil, and clindamycin, respectively. The stability of MEO/clindamycin nanoemulsion (MEO/C NE) with a mean droplet size of 75.46 ± 3.2 nm was monitored over 3 months. The antibacterial activity of MEO/C NE and bulk compounds against E. coli bacterium was compared using a conventional method and a microfluidic chip. A significant difference in the antibacterial activity was observed by employing a microfluidic chip as compared to the conventional technique, probably due to a high contact surface area between the nanodroplets and bacterial membrane. In the microfluidic chip, the E. coli was completely inhibited in 30 min, whereas 3 h was needed for complete inhibition using the conventional method. The results of this study highlight the significance of nanoemulsion delivery systems to improve the antimicrobial activity of clindamycin and also microfluidic technology as a fast and reliable technique for examining antibiotics and nano delivery systems against microorganisms.