Spiraea prunifolia Sieb. et Zucc. var. simpliciflora Nakai (SSN) has been used for the anti-inflammation in traditional folk medicine. To compare water and methanol extracts of SSN, we analyzed major components using LC IT TOF MS. The major components of hot water extract were identified as caffeic acid and p-coumaric acid, but methanol extract was not well established. However, methanol extract was detected with less polarity compounds compared to hot water extract. Next, we investigated the inhibitory effects of SSN water extract on the lipopolysaccharide (LPS)-induced inflammatory response or H2O2-induced oxidative stress in Raw 264.7 macrophage cells. SSN strongly suppressed the production of nitric oxide in LPS-induced inflammatory response without cytotoxcity. The SSN possessed free radical scavenging activities such as DPPH (IC50=320.2 ㎍/㎖), ABTS (IC50=124.0 ㎍/㎖), and superoxide anion radical (IC50=122.6 ㎍/㎖). The total phenol and flavonoid content of SSN was 56.7 ㎎/g, and 15.1 ㎎/g, respectively. Furthermore, SSN decreased the H2O2-induced cytotoxicity by enhancing the cell viability, and SSN significantly reduced the intracellular reactive oxygen species (ROS) level. Therefore, SSN may be recommended as an effective strategy to prevent and/or treat various inflammation and ROS-induced diseases.