Drug‐coated balloons (DCBs) have now emerged as a promising approach to treat peripheral artery disease. However, a significant amount of drug from the balloon surface is lost during balloon tracking and results in delivering only a subtherapeutic dose of drug at the diseased site. Hence, in this study, the use of dextran sulfate (DS) polymer was investigated as a platform to control the drug release from balloons. An antiproliferative drug, paclitaxel (PAT), was incorporated into DS films (PAT‐DS). The characterizations using SEM, FT‐IR, and DSC showed that the films prepared were smooth and homogenous with PAT molecularly dispersed in the bulk of DS matrix in amorphous form. An investigation on the interaction of smooth muscle cells (SMCs) with control‐DS and PAT‐DS films showed that both films inhibited SMC growth, with a superior inhibitory effect observed for PAT‐DS films. PAT‐DS coatings were then produced on balloon catheters. The integrity of coatings was well‐maintained when the balloons were either deflated or inflated. In this study, up to 2.2 µg/mm2 of PAT was loaded on the balloons using the DS platform. Drug elution studies showed that only 10 to 20% of the total PAT loaded was released from the PAT‐DS coated balloons during the typical time period of balloon tracking (1 min) and then ∼80% of the total PAT loaded was released during the typical time period of balloon inflation and treatment (from 1 min to 4 min). Thus, this study demonstrated the use of DS as a platform to control drug delivery from balloons. © 2015 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1416–1430, 2016.