In this work, a dual-mode stimulus chip with a built-in high voltage generator was proposed to offer a broad-range current or voltage stimulus patterns for biomedical applications. With an on-chip and built-in high voltage generator, this stimulus chip could generate the required high voltage supply without additional supply voltage. With a nearly 20 V operating voltage, the overstress and reliability issues of the stimulus circuits were thoroughly considered and carefully addressed in this work. This stimulus system only requires an area of 0.22 mm2 per single channel and is fully on-chip implemented without any additional external components. The dual-mode stimulus chip was fabricated in a 0.25-μm 2.5V/5V/12V CMOS (complementary metal-oxide-semiconductor) process, which can generate the biphasic current or voltage stimulus pulses. The current level of stimulus is up to 5 mA, and the voltage level of stimulus can be up to 10 V. Moreover, this chip has been successfully applied to stimulate a guinea pig in an animal experiment. The proposed dual-mode stimulus system has been verified in electrical tests and also demonstrated its stimulation function in animal experiments.