Fast-growing environmental concern has made nanotechnology surge as an enhancer of eco-friendly materials. In this research, biodegradable and active nanocomposites are developed from thermoplastic starch films with the incorporation of different concentrations of zinc oxide nanoparticles eco-friendly synthesized with starch (ZnONP) (0, 0.5, 1, 2, and 5 wt.%) by flat-die extrusion. ZnONP at 2 and 5 wt.% enhances Young's modulus (E), strain at break (𝝐 b ), and tensile toughness (T), and decreases the water solubility (WS) and moisture content (MC), also inhibiting the growth of Escherichia coli. Additionally, with 5 wt.% of nanofiller, a hydrophobic material with UV-A and UV-B shielding is also achieved. Furthermore, all films are fully biodegraded in vegetal compost at around 4 weeks. The results show that ZnONP can be a very promising alternative as a reinforcing and active agent for preparing new starch-based nanocomposites for the food packaging and coating industry.