This work proposed a programmable pulsed radio-frequency (PRF) stimulator for trigeminal neuralgia (TN) relief on demand. The implantable stimulator is a miniaturized micro-system which integrates a wireless interface circuit, a sensor interface circuit, a PRF pattern generation circuit and a logic controller. The multifunctional stimulator capable of delivering current/voltage stimulation provides the choice of the biphasic sinusoidal, square and patterned waveform for PRF treatment researches. The external handheld device can wirelessly transmit the parameters of frequency, amplitude, pulse duration and repetition rate of the pulse train to the implanted stimulator. While stimulating, the temperature sensor can monitor the operating temperature. The feedback signal is transmitted in medical implanted communication system (MICS). The micro-system is fabricated in a 0.35 μm CMOS process with a chip size of 3.1 × 2.7 mm2. The fabricated chip was mounted on a 2.6 × 2.1 cm2 test board for studying the in vivo efficacy of pain relief by PRF. Animal studies of PRF stimulation and commonly-used medication for trigeminal neuralgia are also demonstrated and the presented results prove that PRF stimulation has greater effectiveness on trigeminal neuralgia relief comparing to the medication. The effectiveness period lasts at least 14 days. The results of neural recording show that the PRF stimulation of trigeminal ganglion (TG) attenuated neuron activities without being severely damaged. Pathology also revealed no lesion found on the stimulated area.