Microcantilevers, as a class of micro-electromechanical system (MEMS) sensors, exhibit remarkable sensitivity and are widely applied in environmental, physical, and biological sensing. In this work, we present the development of a highly sensitive microcontroller-based microcantilever sensor measurement system, leveraging the advantages of direct digital synthesis (DDS) technology to enable real-time, precise, and repeatable measurements. The system integrates an AD9850 DDS module with an Arduino Nano V3 to generate and control a 0.5-V amplitude sine wave signal, amplified to approximately 10 V to actuate a piezoelectric element coupled to the microcantilever. The oscillatory response of the microcantilever is detected using a Wheatstone Bridge circuit, followed by signal rectification and digital conversion via the ADS1115 analog-to-digital converter (ADC). By combining hardware and software innovations, including real-time monitoring via Python, the system allows continuous tracking of the microcantilever’s resonance frequency, achieving a mass sensitivity of 7.66 pg/Hz, a high signal-to-noise ratio (SNR) of 82.5 dB, and demonstrating good repeatability. Integrating DDS technology with microcontroller-based control significantly advances MEMS sensor design, offering broad potential for diverse sensing applications. © 1963-2012 IEEE.