An optical/potential CMOS image sensor was designed and fabricated for bioimaging applications. The image sensor is capable to simultaneously sense an optical image and an on-chip potential image. Target applications of the sensor are on-chip (optical + potential) neural imaging and on-chip DNA microarray sensing. The sensor has a QCIF (176 × 144) pixel array with alternatively aligned optical/potential sensing pixels. The pixel size is 7.5 μm × 7.5 μm. The potential resolution is confirmed to be better than 10 mV. An on-chip fluorescence imaging of a mouse's hippocampus was performed to demonstrate that fluorescence imaging is possible with on-chip configuration.