Amphiphilic copolymers with self-assembling properties produce micelles in aqueous solutions and are made of two hydrophilic and hydrophobic segments. The objective of this study was optimization of the production of folate-conjugated dextran/retinoic acid (DEX/RA) micelles of doxorubicin. Micelles were prepared by direct dissolution method, and different effective parameters on their production were studied by a Taguchi design. The studied variables included CMC of the copolymer, polymer and drug contents, DEX Mw, stirring time, and rate and temperature. The effects of variables on responses of particle size, polydispersity index, zeta potential, drug loading, and release efficiency were studied. The most effective factors on particle size were DEX Mw, CMC of the copolymer, and stirring rate. Zeta potential and drug loading were more affected by the polymer content, DEX Mw, stirring time, and drug concentration. Stirring time and rate and also temperature of water were more effective variables on drug release rate. The optimum processing situation for micelles formation was obtained by copolymers with CMC <17 μg/mL and prepared from 20.1 mg copolymers of DEX Mw of 10000 and drug concentration of 15.9%. The optimized temperature for micelles formation was 40.7°C, and stirring time was 1 hr at a rate of 560 rpm.