The current chapter overview to explain the synthesis of three important class of diazoles namely, pyrazoles, hydroxypyrazolines, and imidazoles followed by elucidation of structure by single-crystal X-ray crystallography, liquid state 1H and density functional theory (DFT) calculations. Our principal interest is focused on the relationship between molecular and/or crystal structure of the synthesized compounds and their efficacy as pharmaceutical drug molecules. Furthermore, they play a significant role as crucial synthetic intermediates. The synthesized molecules were tested for their biological activities like anticancer, antimicrobial, anti-inflammatory, analgesic and antioxidant agents. Strong intermolecular interactions mediated by hydrogen bonding C-H·O or p-p stacking has been observed in X-ray structures most of the molecules. DFT calculations of the NMR chemical shifts for the unambiguous structural assignments of the molecules were performed. Overall, a multidimensional approach has been used for rational design, synthesis and structural characterization of these biologically important molecules. The main goal of this chapter is to review our recent progress in this field.