Micro-opto-electro-mechanical systems (MOEMS) biosensors are employed in various applications such as disease monitoring, drug investigation, detection of pollutants, and biological fluid studies. In this paper, a novel MOEMS biosensor based on a differential folded-flexure structure is introduced. The designed device is employed to detect prostate-specific antigen (PSA) protein and Hepatitis DNA. The target molecules cause a mechanical deflection in the folded-flexure; subsequently, the transmitted optical power across the finger, attached to the flexure, is modulated in proportion to the input concentration. Then, a photodiode power sensor measures the modulated optical power, where the output of the sensor is simply a current related to the target molecules’ concentrations. The employed readout circuit operates at a wavelength of λ = 1550 nm with a laser power of 1 µW. The dimensions of the proposed biosensor are considered to be 365 × 340 × 2 μm³, making this sensor small enough and suitable for integration. The designed biosensor provides notable features of mechanical deflection sensitivities of 0.2053 nm/(ng/ml) and 7.2486 nm/nM, optical transmittance sensitivities of 0.535504 × 10−3 1/(ng/ml) and 18.91 × 10−3 1/nM, total output sensitivities of 0.5398 (mA/W)/(ng/ml) and 19.059 (mA/W)/nM, and measurement ranges of 0-1000 ng/ml and 0-28.33 nM for PSA and Hepatitis DNA, respectively. The proposed system is a sensitive and powerful sensor that can play an important role in diagnosing many diseases.