Plants are a rich source of chemical compounds which serve as food, colors, fragrances’, flavors, medicines, etc. Plant secondary metabolites are widely used in food technology, industry, and medicinal preparations and play a vital role in plant-environment interactions. These metabolites have unique characteristics which make them as important candidates for discovery of new drugs and “lead” molecules. So far the major lacuna in the area of plant metabolite research is the identification and characterization of the secondary metabolites and their biosynthetic mechanisms. With an upsurge in the demand for plant metabolites, the advanced “omics technologies” are most sought after for a faster research and better characterization of the natural products. With the advent of the advanced bioinformatics, genomics, and proteomics and the synergy between combinatorial chemistry and structure-based drug design, the process of characterizing secondary metabolites as lead molecules for drug design has been revolutionized. The scientific community is now witnessing a newer, faster, and sophisticated approach to drug discovery with the aid of in silico characterization methods. This chapter, thus, focuses on the general steps to be followed in the in silicocharacterization of plant secondary metabolites, starting from literature mining, virtual screening, structural characterization, ADMET screening, and structure-based drug designing.