The low-cost, simple, and rapid quantitative assay of eco-friendly magnetic nanoparticles is crucial for advancing sustainable and magnetic-based immunoassay platforms. Therefore, this study aimed to synthesize Fe3O4/SiO2 nanocomposites through a green approach using Moringa oleifera leaf extract and evaluate the performance as magnetic labels for a magnetoresistive sensor. The results showed that the transmission electron microscope produced nearly spherical nanoparticles of 12–15 nm, with SiO2 coating enhancing dispersion and reducing agglomeration. Elemental analysis confirmed the presence of Fe, O, and Si without detectable impurities, while optical measurements showed a blue shift in absorption attributed to quantum size effects. The nanocomposites showed soft ferromagnetic behavior with low coercivity and remanence. A progressive decrease in saturation magnetization (Ms) and magnetic susceptibility was observed with increasing SiO2 content, attributed to the non-magnetic nature of SiO2. This reduction decreased responsiveness to the external magnetic field while enhancing colloidal stability, a key factor for biosensing performance. The sensing performance was evaluated using a giant magnetoresistance (GMR) and tunneling magnetoresistance (TMR) sensor. As a comparison , the GMR single-chip showed a sensitivity of 3.24 mV/(mg/mL) with a low detection limit of 0.76 mg/mL, which decreased with increasing SiO2 content. The TMR single-chip showed higher sensitivities overall, reaching 6.68 mV/(mg/mL) for pure Fe3O4 and maintaining strong responses (6.16–4.22 mV/(mg/mL)) with SiO2-coated samples. Meanwhile, the GMR double-chip configuration further improved linearity and signal stability compared to the single-chip system, showing significant potential for enhancing reproducibility in biosensing applications. The sensor showed rapid detection of 30 s, good linearity, and stable responses over repeated measurements. These results emphasize the potential of green-synthesized Fe3O4/SiO2 nanocomposites to accelerate the development of next-generation portable, cost-effective, and eco-friendly biosensing devices for biomedical and environmental monitoring. © 2026 Vietnam National University, Hanoi.