In recent years, studies have increasingly recognized that many natural products with biological activity have been isolated from marine organisms, while the chemical structures are very different from those of land-based organisms. Therefore, the ocean is a natural drug source. Regarding drug screening, anti-inflammatory activity has become a key point, and many studies confirm that inflammation plays an important role in many human diseases. Many different compounds are now in the clinical evaluation stage. However, the inflammation-related diseases being closely linked, there is an urgent need to study the anti-inflammatory effects as well as screen the therapeutic drugs for research and development. In this study, we isolated and purified compounds from Formosan gorgonian (Briareum excavatum) and Formosan soft coral (Lobophytum sarcophytoides) and investigated biological activities. We confirmed that the natural compound Brei from B. excavatum and the compounds Sac-1 and Sac-2 from L. sarcophytoides produced significant inhibition of the proinflammatory proteins inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the lipopolysaccharide (LPS)-induced murine macrophages (RAW 264.7) cell model. We examined in vivo whether the B. excavatum Brei has anti-inflammatory and antinociceptive effects by using the carrageenan-induced inflammation model. Using the paw-edema assay, we performed several important investigations such as the plantar analgesia test, mechanical hyperalgesia test (allodynia), and weight-bearing analysis of animal behavior to evaluate the degree of pain and inflammation. Our results demonstrate that the natural product Brei can reduce paw-pad swelling, thermal hyperalgesia, threshold latency, and improve the affected limb in the carrageenan-induced inflammatory model. In the histopathology analysis, we showed that Brei significantly inhibited the aggregation and infiltration of inflammation-related blood cells and improved the inflammatory status of the tissues. Therefore, the marine natural compound Brei has anti-inflammatory activity and it can be used as a therapeutic compound for acute inflammation in the near future.