Oleoresin capsicum (OC) is an extract of chili pepper containing the active agent capsaicin. In this study, OC-loaded nanoemulsions were prepared by microfluidization and stabilized with sucrose monopalmitate (SMP) and lecithin. The difference in size and distribution of droplets determined the nanoemulsion behavior mainly due to the interaction of emulsifiers between oil and aqueous phase. The hydrophilic interaction between SMP and aqueous phase and the hydrophobic interaction between lecithin and oil phase were monitored with NMR relaxometry. OC nanoemulsion fabricated with SMP showed the best transparency with smallest droplet size (around 34nm) and stable with glycerol after 28days at ambient storage. Lecithin containing nanoemulsions showed improved bioactivity as showing antioxidant (0.82mg DPPH/L) and antimicrobial (3.40 log for Escherichia coli and 4.37 log for Staphylococcus aureus) activity. Finally, results have important implications to determine the appropriate formulation conditions for OC with food-grade surfactants to be used in pharmaceuticals and food industry.