The most traditional and popular agents are non-steroidal anti-inflammatory drugs (NSAIDs). However, due to their side effects on different organs. In this review, several compounds created as acetamide derivatives to maintain their anti-inflammatory properties, selective COX-II inhibitors, are discussed. Numerous literature reviews have highlighted the significance of these anti-inflammatory heterocyclic compounds in treatments, taking into consideration the significance of this pharmacological class. Cyclooxygenase-II (COX-II) inhibitors can be used in a wide variety of applications thanks to the prodrug method. It plays a big part in drug development. Many researchers have created different prodrugs using acetamide molecules to adjust pharmacokinetic parameters, enhance organoleptic qualities, or increase chemical properties. A huge quantity of amide derivatives belonging to different classes of compounds exhibit cyclooxygenase-II inhibitors and mainly to treat arthritis, pain, menstrual camps, and colonic polyps, they used for relief of pain, fever, swelling, and tenderness. Finally, the nanoparticles of cyclooxygenase (II) inhibitors were used for improving the efficacy.