Chronic periodontitis is one of the most common oral diseases worldwide and the excessive local reactive oxygen species (ROS) level of periodontitis aggravates the destruction of periodontal tissue. Scavenging ROS and restoring local ROS levels in inflammation tissues has exhibited promising treatment prospects. Tea polyphenol-derived functional nanomaterials often serve as ROS scavenger in inflammatory disease for their antioxidant and anti-inflammation ability. However, the therapeutic effect of tea polyphenol resources remains unsatisfactory due to the tedious encapsulation, poor stability, and low operational bioactivities. In this work, functionalized epigallocatechin-3-gallate (EGCG, green tea derivative) nanoparticles (NPs) were developed via a one-step polyphenolic condensation reaction. The resulting nanoparticles are capable to maintain the stability of epigallocatechin gallate, featuring excellent anti-oxidation capacity. The EGCG NPs can scavenge ROS effectively, and down-regulate the expression of pro-inflammatory cytokines by reprograming macrophages from M1 to M2 phenotype. In vivo results illustrate that EGCG NPs can inhibit the alveolar bone loss from 1346.8 ± 244.9 μm to 596.1 ± 92.1 μm via decreasing ∼50% ROS level, as well as reduce osteoclastic activity in a rat model of chronic periodontitis. Therefore, this EGCG NPs provides an effective and safe antioxidant defense platform for chronic periodontitis therapy.