Abstract This work reports studies on the production of eugenol-loaded microspheres by solvent evaporation method, targeted for incorporation into textile substrates, using different cellulose derivatives: ethyl cellulose, cellulose acetate (CA), cellulose butyrate acetate, and cellulose acetate phthalate. The microspheres were evaluated in terms of size, shape, thermal stability, encapsulation efficiency, and eugenol kinetics release. CA-based microspheres proved to be the best, thus being selected for subsequent experiments. Comparable properties of the CA-based microspheres were achieved ongoing from 100 mL to higher batch volumes (up to 2000 mL). The eugenol-loaded microspheres were successfully incorporated into cotton fabrics using a padding technique, confirmed by FE-SEM. Eugenol release profiles from the impregnated textiles demonstrated a slow and controlled release (less than 20% of the encapsulated amount over 90 days). The developed microspheres demonstrated to be the most promising for the retention and protection of hydrophobic active compounds for possible textile applications. Graphic abstract