Non Steroidal Anti-Inflammatory Drugs (NSAIDs), are widely used as first line of defense against most of acute and chronic inflammatory diseases. However, in spite of their apparent safer profile, as compared to steroids, they can also drive into moderate and severe reactions. Since the very beginning foremost concerns have been focused on the Gastric Damage coming from the inhibition of COX-1 derived prostaglandins, which were found to play a fundamental protective action on the overall stomach homeostasis. Thereafter indeed, most efforts to improve NSAIDs therapeutic proficiency were aimed at counteracting upper Gastrointestinal (GI) adverse reactions.