Low dose mixing and its optimization process parameters are facing more challenges. Moreover, minor variation in a dose will tend to significantly have a huge impact on the products’ performance including safety and efficacy of the dosage form. Hence, the characterization in every stage of product development of a low dose compound is mandatory. For this purpose, glimepiride and metformin in the ratio of 1:500 was formulated into tablet deciphering a fixed-dose combination product. The tablet was prepared by wet granulation method and optimized by time-dependent random mixing. Confocal Raman microscopy was employed for the present work for evaluation of compatibility studies, in-process and post-compression parameters. Further, the microscopical evaluation was done for the particle scout analysis. The obtained results indicated that the powder blend was compatible and provided uniform mixing in 20 min. Microscopical evaluation has shown that glimepiride still existed in the amorphous state even after compression. Moreover, the glimepiride area in the single-layer was found to be 0.06%. With this, we propose that confocal Raman microscopy plays the promising role in the detectability of the glimepiride. Therefore, in future, the layer by layer analysing can be opted to study the entire spatial arrangement of the API and excipients, which may tend to have a better understanding of dissolution and their related parameters.