Robust and flexible free-standing polymer films for unidirectional drug delivery are fabricated by sandwiching drug-containing polyelectrolyte multilayer films between poly(lactic-co-glycolic acid) (PLGA) barrier and capping layers. The drug-containing films are fabricated by layer-by-layer (LbL) assembly of chemically cross-linked poly(allylamine hydrochloride)-dextran (PAH-D) microgel and hyaluronic acid (HA), which can load negatively charged cancer-inhibiting drug, methotrexate (MTX). Because the PLGA barrier layer effectively blocks MTX release, MTX can be predominantly released from the PLGA capping layer of the free-standing film. This increases the efficacy of released MTX to cancer cells while minimizing its side effects on the normal tissues. We believe that the unidirectional drug delivery free-standing films can open a new avenue to design of highly efficient drug delivery systems for biomedical application.