A dual-configuration dual-mode stimulator for neuro-modulation is proposed and designed. All the electrical stimulation patterns that frequently used for neuro-modulation can be generated by the proposed stimulator chip. Dual-configuration represents the bipolar or monopolar structure, meanwhile dual-mode stands for the current or voltage output. No matter what stimulation circumstance is chosen, biphasic or monophasic waveforms can be fully supported by the proposed stimulator chip. The stimulator chip with 4 stimulation channels has been fabricated in 0.18-μm 1.8-V/3.3-V low-voltage CMOS process with common grounded p-type substrate, which is suitable for SoC integration. The design has conquered the overstress and reliability issues in the low-voltage transistors under the negative voltage power domain. Each channel in the stimulator chip only occupies the silicon area of 0.052 mm2, and the maximum output level of stimulus amplitude is up to ±3.6 mA and ±3.6 V. With the built-in discharge function, bio-safety concern of unbalanced charge in neuro-stimulation can be dealt with properly. Moreover, the proposed stimulator chip has been applied on both imitation measurement and in-vivo animal test successfully.