We report the quantification/monitoring of glucose levels in a blood sample using optical diffuse reflectance (ODR) underlying variations in optical parameters with a white light source (at peak wavelength ∼600 nm and range 450–850 nm) and in blood in vivo using M-mode optical coherence tomography (OCT) in terms of the translational diffusion coefficient (DT). In the ODR experiments, we have investigated two types of mono-dispersive particles, i.e. polystyrene microspheres (PMSs) with diameters of 1.4 μm (variable concentrations) and 2.6 μm (fixed concentration) in a water phantom by observing changes in the reduced scattering coefficient. We believe that these differences in optical properties will be helpful for the understanding and optimal use of laser applications in blood glucometry without piercing the skin. In the OCT experiments, this idea of glucose monitoring was applied on an in vivo normal mouse without injection of glucose intravenously to provide the threshold levels by envisioning/identifying a blood vessel by speckle variance (SV-OCT) using a dorsal skinfold mouse windows chamber model. We report an average value of translation decorrelation time τT = 41.18 ± 1.92 ms and DT = 8.90 × 10−14 m2 s−1 underlying the dynamic light scattering (DLS). Our results have a potential application in the quantification of higher glucose levels in vivo administrated intravenously.