To determine the effect of triclosan-containing fluoride toothpaste on the clinical parameters and the osteo-immunoinflammatory mediators in the peri-implant fluid when applied in a stent during experimental peri-implant mucositis in smokers. Materials and methods Twenty-six smokers with an implant-supported crown were enrolled in this double-blind, randomized, crossover study. During the two 3-week periods without mechanical toothbrushing (washout period: 30 days), patients were randomly assigned to triclosan/fluoride (n:13) or fluoride toothpaste (n:13), three times/day. Clinical and immunoenzymatic assays were performed at baseline, 3, 7, 14 and 21 days. Results Both groups showed increase in the Plaque Index throughout the study (p = 0.001), without inter-group differences at 21 days (p > 0.05). No intra- or inter-group differences were observed for IFN-gamma, IL10, IL-1 beta, IL8, IL-17, IL-6, TNF-alpha, MMP-2, MMP-9, TGF-beta, OC, OPN, ICTP, OPG and RANKL (p > 0.05). However, the RANKL/OPG ratio was significantly higher in fluoride toothpaste-treated sites when compared to triclosan/fluoride-treated sites at the end of period without mechanical toothbrushing, on the 21st day (p = 0.041). Conclusion Triclosan-containing toothpaste favorably modulated osteo-immunoinflammatory mediators during the experimental peri-implant mucositis in smokers, decreasing the ratio of RANKL/OPG Ver menos