The assembly of low-fouling polymer capsules with redox-responsive behavior and intracellular degradability is reported. Thiol-containing poly(2-ethyl-2-oxazoline) (PEtOxMA(SH)) brushes are synthesized by atom transfer radical polymerization (ATRP) of oligo(2-ethyl-2-oxazoline)methacrylate and glycidyl methacrylate (GMA) and subsequent ring-opening reaction of the GMA. Sequential deposition of PEtOxMA(SH)/poly(methacrylic acid) (PMA) multilayers onto silica (SiO2) particle templates and crosslinking through disulfide formation yield stable capsules after the removal of the SiO2 templates by buffered hydrofluoric acid (HF). The redox-responsive nature of the disulfide crosslinking groups enables the degradation of these capsules under simulated intracellular conditions at pH 5.9 and 5 mm glutathione (GSH). Furthermore, capsule degradation is observed after incubation with dendritic (JAWS II) cells. Even at high capsule-to-cell ratios, PEtOxMA(SH) capsules show only negligible cytotoxicity. Quartz crystal microgravimetry (QCM) studies, using 100% human serum, reveal that films prepared from PEtOxMA(SH) exhibit low-fouling properties. The degradation and low-fouling properties are promising for application of PEtOxMA(SH) films/capsules for the delivery and triggered release of therapeutics.