Rubus buergeri Miq., a wild species native to Jeju Island (Republic of Korea), is a relatively understudied plant with potential as a source of bioactive phenolic compounds. This study investigated the phytochemical composition of R. buergeri extract (RBE) and evaluated its antioxidant and anti-inflammatory activities using a bioactivity-guided fractionation approach. Antioxidant capacity was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and ferric reducing antioxidant power assays (FRAP), along with total phenolic content determination, while anti-inflammatory activity was evaluated by measuring nitric oxide (NO) production and inflammatory gene expression in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. RBE exhibited high phenolic content and strong antioxidant activity; its ethyl acetate and n-butanol fractions demonstrated the greatest antioxidant activities and significantly inhibited LPS-induced NO production. Furthermore, RBE suppressed LPS-induced mRNA expression of Nos2, Ptgs2, Tnfa, Il1b, and Il6, indicating coordinated inhibition of inflammatory responses. Ultra-high-performance liquid chromatography (UHPLC) analysis identified ellagic acid, ethyl gallate, and epicatechin as major phenolic constituents, with ellagic acid and ethyl gallate showing stronger inhibitory effects on NO production and inflammatory gene expression than epicatechin. These findings suggest that the phenolic constituents of R. buergeri modulate NO-associated inflammatory responses and support its potential as a source of anti-inflammatory phytochemicals.