The sensors based on ion transport in a confined nano-/microchannel (i.e., iontronic sensors) have brought new opportunities for in vivo neurochemical assay, especially for electroinactive molecules. However, the interference on spontaneous neuronal activity induced by the electric field around the sensors has not been addressed. Here, the electric field distribution with a double-barreled micropipette was shrunk and quantified by finite element simulation, which can explain and minimize the influence on spontaneous neuronal activity. The parameters affecting the electric field distribution, including the pore size, applied voltage, and angle degree, were studied to balance the sensitivity and interference on spontaneous neuronal activity. The double-barreled micropipette, as a pH sensor with high selectivity and sensitivity, has been successfully applied to real-time pH sensing in rat brain. This study offers a new way for in vivo monitoring neurochemical dynamics with neuron-compatibility.