Herein, we report an improved minimum detectable displacement on a surface stress biosensor using optical interferometry, allowing for the detection of a low biomarker concentration via antigen-antibody reaction. The sensor is composed of a submicronthick freestanding polymethyl methacrylate (PMMA)/parylene-C membrane on a polydimethylsiloxane (PDMS) substrate with a microcavity to generate optical interference. The cavity structure was fabricated by transferring the submicron-thick bilayer to the highly adhesive PDMS substrate. The detection of human serum albumin antigen at a concentration of 1 pg/mL was achieved by antigen-antibody reaction using simultaneous optical and electrical measurements. In addition, the minimum detectable displacement of the optical interferometric surface stress sensor was determined to be 42.6 pm, representing an 11.7-fold improvement compared with conventional cantilever-based surface stress sensors.