Periodontitis induced by chronic subgingival infection is a ubiquitous disease that causes systemic inflammatory consequences and poses a negative impact on quality of life. The disease is treated and potentially prevented by patient's self-care aimed at eliminating the oral pathogens from the region. Currently available products for interdental self-care, including dental floss and interdental brush, have limited ability to prevent the disease. Here, we report a coated dental floss thread, termed "nanofloss," which uses polyphenol-based nanocoating to functionalize the floss thread with therapeutic agents. Multiple therapeutics can be integrated into the nanofloss including antibacterial small molecules and proteins. Flossing with nanofloss-delivered therapeutic agents to the challenging subgingival region with long-term retention even against the flushing action of the oral fluid in vivo. Our in vitro and in vivo studies demonstrate that chlorhexidine gluconate-loaded nanofloss effectively treats the subgingival infection by Porphyromonas gingivalis. Collectively, the nanofloss offers a promising and easily usable tool for targeted self-care of subgingival infection against periodontitis.