Inflammation represents an initial response of immune system and is involved in a number of biochemical incidents. Such incidents may multiply and further develop the provocative response. Over the past 15 years, various classes of secondary metabolites that were isolated from plant and marine sources have been described as natural cyclooxygenase (COX) inhibitors. The majority of natural COX inhibitors could be used as a selective therapeutic agent for complementary medicine and clinical applications. Currently, the inflammation is commonly treated by non-steroidal anti-inflammatory drugs (NSAIDs), several medications of which, however, have been linked to renal and gastrointestinal side effects. A variety of inhibitors of COX-2 that are selective (celecoxib, rofecoxib, valdecoxib and others) have been designed as NSAIDs mostly with enhanced stomach safety profiles. This helps to improve the compliance and functions in the geriatric patients as they have so many complications and problems associated with the diseases. The use of complementary medicine in combination with clinical therapy might give better results than medicine alone. Some disease condition like cancer which shows the COX-2 expressions could also have treatment related problems in such cases the selective inhibitors used as a complementary medicine. On the other hand, elevated cardiovascular risks have brought increasing worries about the safety of using specific inhibitors of COX-2. This current review focuses on how quinoline heterocycle was used for creation of inhibitors of COX-2 since 2009 along with its clinical significance in complementary medicine. These agents included the variety of substituents on the ring or ring attached to other heterocycles. As a result, the quinoline heterocycle will be used for creating and finding anti-inflammatory COX-2 medicines.