Edible films containing natural antimicrobials, like natamycin and nisin, constitute an emerging technology that provides an additional stress factor for food preservation. However, it has been observed that edible films based only on tapioca starch present several failures, such as poor mechanical properties and low hydrophobicity. Pumpkin and oat bran are ingredients that provide multiple health benefits. In this work, it was intended to improve mechanical properties and hydrophobicity of tapioca starch edible films, containing natamycin and nisin, by the addition of pumpkin peel, pumpkin mesocarp or oat bran fillers. In turn, the effect of fillers on the films was evaluated through the evaluation of their color, water vapor permeability, morphological characteristics, and microbiological behavior. Results showed that pumpkin fillers improved mechanical properties, reducing the strain at break and increasing the stress at break of tapioca starch edible films. Particularly, pumpkin peel filler increased 36 times the firmness of tapioca starch films, reaching a value of 87.64 MPa. Also, this filler increased 300% the hydrophobicity of the films with a contact angle of 48.29°. The incorporation of all studied fillers allowed the normal diffusion of natamycin. However, the different fillers retained the nisin in different degrees and, particularly, oat bran filler was the one with the highest affinity for it. After evaluating all the studied properties, it can be concluded that the composite film filled with pumpkin peel, is an improved version to the one without it, for food packaging.