Biosensors play a pivotal role in biomedical research and clinical diagnostics, offering high specificity and sensitivity in analyte detection. Despite the tremendous research efforts and advancement in recent years, the current biosensor technology still faces challenges such as high cost, overt complexity, susceptibility to interference. Herein, a multimodal, biomaterial-based biosensor platform is developed by infusing poly(ethylene glycol) (PEG) hydrogel with multiferroic nanoparticles (MFP), capable of highly sensitive and quantifiable tuning of both electric polarization and magnetization upon analyte interaction due to their strong magnetoelectric coupling at room temperature. The PEG hydrogel acts not only as a mechanically compliant platform in which MFP can be stably dispersed and integrated but also modified to present antibodies to target specific protein analytes while minimizing nonspecific interaction. The MFP-PEG hydrogel is shown to demonstrate highly sensitive and consistent changes in both ferroelectric and ferromagnetic properties analyte detection down to femtomolar range in both in vitro and in vivo analyses, effectively demonstrating the efficacy and versatility of MFP-PEG hydrogel for diagnostic and biomedical applications.