In this work, based on advanced gate-all-around (GAA) technology, the extended sensing gate (ESG) GAA Si nanosheet (SiNS) ion sensitive field effect transistor (ISFET) sensor was fabricated and reported for the first time. Due to the GAA structures and the vertically-stacked SiNS channels, the average sensitivity of the ESG GAA SiNS ISFET sensor can be reached 58.8 mV/pH, which provides good gate control and ultra-sensitive detection capabilities. In addition, the actual minimum detection concentration of C-reactive protein (CRP) by ESG GAA SiNS ISFET sensor in 1$\times$ PBS environment is as low as 100pg/mL, which is much lower than the normal concentration of human body.