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 submicron-thick 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.