Transitional metal oxide has a significant role in developing biosensors due to the flexibility for structural modification with a large surface area that facilitates more electron transfer between the analyte and sensor surface, leading to improved sensor performance. The titanium dioxide (TiO2) and zinc oxide (ZnO) nanostructures exhibit intrinsic peroxidase-like activity and have been potential catalysts for various biosensors. In this study, non-enzymatic glucose biosensors were fabricated based on multiple combinations of TiO2 nanoparticles, 3D structures ZnO nanoflowers (ZNFs), reduced graphene oxide (rGO), iodine, and carboxyl methylcellulose (CMC). The developed nanocomposites were characterized by X-ray diffraction, X-ray photoelectron spectroscopy, field emission scanning electron microscopy, high resolution-transmission electron microscopy, energy-dispersive X-ray spectroscopy spectrum, ATR-Fourier transforms infrared, Raman spectroscopy, photoluminescence emission spectra, dynamic light scattering, and zeta potential. The developed TiO2/I2/CMC nanocomposite (TIC) film for non-enzymatic colorimetric glucose detection had a minimum detectable concentration (LOD) of 0.4 mM with a wide linear range (0.5 to 10 mM) at room temperature and a coefficient of determination (R2) = 0.980 (n=3). The I-rGO@TiO2 (TIR) sensor exhibited a wider linear detection range (0.5―10 mM) at room temperature. The LOD of the sensor was 0.23 µM (S/N=3), and the sensitivity was 221.69 µA mM&minus1 cm&minus2 with a R2 = 0.985 (n=3). The ZNFs@TiO2/I-PVA/CMC (ZTIPC) hybrid film was developed to detect glucose in human saliva. The novel ZTIPC glucose sensor exhibited a LOD of 0.2 mM with R2 = 0.985 (n=3). The ZTIPC sensor had a linear glucose detection range of 0.5―10 mM with a detection limit of 0.2 mM and a limit of quantitation of 0.7 mM. The average fasting and postprandial glucose in human saliva detected by ZTIPC hybrid film was 0.30 ± 2.48 mM and 0.49 ± 0.16 mM, respectively. The ZTIR nanocomposite exhibited a LOD of 0.7 mM and a limit of quantification of 2.3 mM with R2 = 0.985. The enhanced glucose sensitivity of developed nanocomposites was obtained due to the synergistic effect and higher surface-to-volume ratio, providing more active area and narrow bandgap that enhanced the catalytical performance. The structural modification of transitional metal oxides provides a suitable environment for immobilizing molecules and electron transfer charge carriers to enhance catalytic performances suitable for sensing applications.