This paper presents a highly sensitive flexural plate-wave (FPW)-based microsystem for rapid detection of tetrahydrocannabinol (THC) in human urine. First, a circular-type interdigital transducer (IDT) was integrated with a circular-type silicon-grooved reflective grating structure (RGS) to reduce insertion loss. Then, with lower insertion loss (−38.758 dB), the FPW device was used to develop a novel THC biosensor, and the results reveal that this FPW-THC biosensor has low detection limit (1.5625 ng/mL) and high mass-sensitivity (126.67 cm2/g). Finally, this biosensor was integrated with field-programmable gate array (FPGA) board and discrete components for prototyping a FPW readout system, whose maximum error was 12.378 kHz to ensure that the linearity of detection up to R-square is equal to 0.9992.