Hibiscus syriacus L. extract (HSE) traditionally has been recognized as promising natural resources for the treatment of diseases related to hyper-inflammation. This study aimed to investigate the anti-inflammatory effect of HSE in LPS-stimulated Raw 264.7 cells. For this purpose, we determined the optimal extraction method and found that the ultrasonic extraction showed the most effective activity for reduction of free radical species by DPPH assay. Then, we performed PGE2 concentration analysis, COX-2 activity assay, proliferation assay, apoptosis detection, and western blotting analysis. HSE decreased PGE2 concentration and COX-2 activity and reduced the expression of COX-2 and IL6 in LPS stimulated Raw 264.7 cells. In addition, we found that HSE inhibited the proliferation and induced apoptosis with increase in the expression of pro-apoptotic proteins such as caspase-3, -7, -9, Bax, Bim, FOXO3, and p53 in LPS-stimulated Raw 264.7 cells. Taken together, we found that HSE effectively suppressed LPS-stimulated Raw 264.7 cells suggesting that HSE has the potential to treat inflammation via regulation of proinflammatory COX-2, IL6, and PGE2 and induction of apoptosis.