Optical and electrophysiological measurements help us understand mouse brain functions. One type of device available for optical measurements is an implantable complementary metal-oxide-semiconductor (CMOS) image sensor (ICIS). However, an ICIS alone cannot directly measure the electrical signals emitted by mouse brain neurons. Considering this limitation, we have developed an implantable multimodal sensor that can simultaneously make optical and electrophysiological measurements of the neural activity in the brains of mice. The proposed device integrates a CMOS image sensor and a neural amplifier with a recording electrode into a single chip, making it no more invasive than a conventional implantable CMOS image sensor. The proposed device is based on a 0.35-μm CMOS standard process and occupies an area of 0.50 × 5.0 mm2. Furthermore, a hybrid filter is fabricated on the imaging pixel array to remove the excitation light and selectively detect fluorescence. From electrophysiological measurements, we confirm that the neural amplifier features a mid-band gain of 39 dB from 500 mHz to 4 kHz, which is the bandwidth that includes local field and action potentials. Crosstalk noise is observed because of the digital signal used to control the image sensor. However, in vivo experiments demonstrate that the device is capable of simultaneously measuring and processing optical and electrophysiological signals when the amplitude spectrum has a peak of less than 1 μV.