In this study, an I-optimal design was used to select an optimal muña essential oil nanoemulsion (MEO-NE) for application in active starch-based films. Four independent variables were used to optimize the process: emulsifier concentration (X1) (% w/w), sonication time (X2) (min), essential oil concentration (X3) (% w/w), and emulsifier type (X4) (Tween 80 or sapote gum). Results revealed that MEO-NE containing 5.24% of MEO, 6% Tween® 80, and 9 min of ultrasound treatment exhibited a small droplet size (Y1) (48.6 nm), moderate ζ-potential (Y2) (−15 mV), and DPPH inhibition (Y3) (95.6%). Starch-based films were incorporated with optimized MEO-NE at 5% (F1) and 10% (F2) and compared with control films (F0). F1 and F2 exhibited lower moisture content, water solubility, and water vapor permeability than F0; however, their contact angles were higher. The addition of MEO-NE into the polymeric matrix increased the stiffness of F1 and F2; however, the elongation at yield was slightly lower than that of F0, resulting in less stretchable composite films. All films were disintegrated by more than 90% after 5 days of burial under composting conditions. The incorporation of MEO-NE into composite films significantly enhanced their properties, suggesting their potential use as eco-friendly packaging.