AbstractImplant failures are primarily related to bacterial infections and inflammation. Nanocoating of implant devices with organic molecules is a method used for improving their integration into host tissues and limiting inflammation. Bioengineered plant‐derived rhamnogalacturonan‐Is (RG‐Is) from pectins improve tissue regeneration and exhibit anti‐inflammatory properties. Therefore, the aim of this study is to evaluate the in vitro effect of RG‐I nanocoating on human gingival primary fibroblast (HGF) activity and proinflammatory response following Porphyromonas gingivalis (P. gingivalis) infection. Infected HGFs were incubated on tissue culture polystyrene (TCPS) plates coated with unmodified RG‐I isolated from potato pectin (PU) and dearabinanated RG‐I (PA). HGF morphology, proliferation, metabolic activity, and expression of genes responsible for extracellular matrix (ECM) turnover and proinflammatory response were examined. Following the P. gingivalis infection, PU and PA significantly promoted HGF proliferation and metabolic activity. Moreover, gene expression levels of IL1B, IL8, TNFA, and MMP2 decreased in the infected cells cultured on PU and PA, whereas the expression of COL1A1, FN1, and FGFR1 was upregulated. The results indicate that RG‐Is are promising candidates for nanocoating of an implant surface, can reduce inflammation, and enhance implant integration, particularly in medically compromised patients with chronic inflammatory diseases such as periodontitis and rheumatoid arthritis. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3475–3481, 2017.