This invention relates to a dual-frequency ultrasonic transdermal penetration enhancement device, its control method, and its application. The dual-frequency ultrasonic transdermal penetration enhancement device includes: a rectification and voltage regulation unit for adjusting the input power supply voltage to a preset voltage range; a dual-frequency signal generation unit for generating a first frequency signal and a second frequency signal respectively through two sets of DDS waveform generators; an impedance matching unit for adjusting the output impedance to match the input impedance of the ultrasonic transducer; a detection feedback unit for acquiring voltage and current signals and calculating the phase difference and the effective value of the current; and a control unit for obtaining the resonant frequency range of the ultrasonic transducer through frequency sweeping, adjusting the driving frequency when the real-time detected phase difference is too large and causes the transducer to deviate from its resonant state, and adjusting the output power to a stable state based on the error between the effective value of the current and a preset target value. This invention simultaneously increases cavitation effect and promotes molecular diffusion, thereby effectively improving drug transdermal efficiency.