The present study aimed to purify, structurally characterize, and evaluate the anti-inflammatory activity of the polysaccharide extracted from Typha angustifolia. Two purified polysaccharides (PTA-1 and PTA-2) were obtained via DEAE-52 cellulose chromatography. Their structural characterizations and antioxidant activity were in vitro analyzed. To evaluate the anti-inflammatory activity of PTA-2, the levels of inflammatory cytokines, intracellular ROS production, and the inhibitory effects of the transcriptional activation of the nuclear factor kappa B (NF-κB) signaling pathway were determined. PTA-1 comprises glucose (100%) with α-(1 → 3) glycosidic bonds, and PTA-2 comprises glucose (66.7%) and rhamnose (33.3%) formed by β-(1 → 3) glycosidic bonds. PTA-1 and PTA-2 showed strong antioxidant activity in vitro. Moreover, PTA-2 intervention (50, 100, and 200 μg/mL) suppressed the production of inflammatory cytokines, the activation of NF-κB signaling, and reactive oxygen species production significantly. The results identified PTA-2 as a natural product that could be applied in anti-inflammatory drugs.