Cycloxygenase-2 (COX-2) is well established for its role in inflammation, cancer and has also been reported to play a significant role in radiation induced inflammation and bystander effect. It has already been reported to have a role in protection against radiation induced damage, suggesting it to be an important target for identifying novel radiation countermeasure agents. Present study aims at identifying novel small molecules from pharmacopeia using COX-2 as target in silico. Systematic search of the molecules that are reported to exhibit radiation protection revealed that around 30% (40 in 130) of them have a role in inflammation and a small percentage of these molecules (20%; 8 in 40) are reported to act as non-steroidal anti-inflammatory drugs (NSAIDS). Docking studies further clarified that antiinflammatory compounds exhibited higher binding energy (BE). Out of 15 top hits, 14 molecules are reported to have anti-inflammatory property, suggesting the significant role of COX-2 in radiation protection. Further, Johns Hopkins Clinical Compound Library (JHCCL), a collection of small molecule clinical compounds, was screened virtually for COX-2 inhibition by docking approach. Docking of around 1400 small molecules against COX-2, leads to identification of a number of previously unreported molecules, which are likely to act as radioprotectors.