Janus particles with differentially degradable compartments were prepared by electrohydrodynamic (EHD) co-jetting and subsequent controlled crosslinking. These bicompartmental particles are composed of an interpenetrating polymer network of poly(ethylene oxide) and poly(acrylamide-co-acrylic acid) in one hemisphere and a crosslinked copolymer of dextran and poly(acrylamide-co-acrylic acid) segments in the second compartment. The compositional anisotropy caused differential hydrolytic susceptibility: Although both compartments were stable at pH 3.0, selective degradation of the PEO-containing compartment pH 7.4 was observed within 5 days. Janus particles with differentially degradable polymer compartments may be of interest for a range of oral drug delivery applications because of their propensity for decoupled release profiles.