Various nanoparticles have been developed for bio-applications. However, nanocomposites particles, (NCPs) with effective and ability to sensing cholesterol, are still needed. Herein, we present new cholesterol and pH-responsive NCPs as sensor particles to promote sensitivity. The traditional method of mixing and grinding was used to fabricate the oxides of magnesium and manganese MgO–MnO
2
NCPs with different mixing ratios. Structural properties, detection of cholesterol, and pH sensitivity were examined. Results propped the high efficiency of MgO–MnO
2
NCPs compared with individual oxides (MgO and MnO
2
), low response time, while the analytical results confirmed the homogeneous structure of MgO–MnO
2
NCPs. Particle size distribution results for NCPs were within 16.4 to 100 nm, which makes it promising in medical and bio-applications.