This paper reports high performance ion-sensitive field-effect transistors (ISFETs) with a suspended honeycomb nanowire (SHNW) structure. The SHNW can provide a longer, stiction-free channel than that which is possible with a suspended straight nanowire (SSNW) for the realization of gate-all-around biosensors. Devices with SHNWs, SSNWs and conventional nanowires on the substrate have been fabricated using a top-down approach in order to compare their electrical performances. The SHNW devices exhibit excellent electrical characteristics such as lower subthreshold swing, higher transconductance and higher linear drain current. In addition, the SHNW ISFETs show better pH sensitivity than other ISFETs. Based on the results, the SHNW device appears promising for enhancing the intrinsic performance and ensuring the reliable operation of biosensor applications.