Peri-implant mucositis is a bacterial and inflammatory disease of implant surrounding soft tissues. Chlorhexidine (CHX) associated with PVP-VA (Polyvinylpyrrolidone/vinyl acetate) has an adjuvant function in the antibacterial activity: it protects the film-forming layer, due to polymer, from microbial contamination or over-infection, and prolongs its permanence, without a direct action on the tissues and wounds. Sodium DNA is able to improve gingival trophism. The aim of the study was to compare a gel with CHX and antidiscoloration system (A.D.S.) 0.5% with the addition of PVP-VA and sodium DNA with a placebo gel without chlorexidine in peri-implant mucositis treatment. Trial design: A single center randomized controlled pilot clinical trial was conducted on a total of 24 patients with mucositis, randomly allocated into two groups. In the group (A) (n = 12) patients were treated with a gel with CHX + A.D.S. 0.5% while a placebo gel was used in the group (B) (n = 12). Plaque Index (PI) (primary outcome), Bleeding on probing (BOP) and Gingival Index (GI) (secondary outcomes) were assessed at baseline and at 2 weeks after treatment period. Mean PI score recorded at baseline was 2.4 ± 0.4 [95% CI: -2.682/7.482] in the group (A) and 2.2 ± 0.5 [95% CI: -4.153/8.553] in the group (B) (p > 0.05) while mean PI score at 2 weeks was 0.5 ± 0.4 [95% CI: -4.582/5.582] and 1.7 ± 1.9 [95% CI: -9.736/13.14] in the group and in the group respectively (p < 0.05). Mean BOP value at baseline was 57.1 ± 15.2% [95% CI: -136.0/250.2] in the group (A) and 55.3% ± 11.7% [95% CI: -93.36/204.0] (p > 0.05) while mean BOP value at 2 weeks follow-up was 14.3% ± 6.6% [95% CI: -69.56/98.16] (A) and 45.4% ± 9.8% [95% CI: -79.12/169.9] (B) respectively (p < 0.05). A significant reduction in gingival inflammation indexes was found at 2 weeks in patients with peri-implant mucositis treated with a gel with CHX + A.D.S. 0.5% with the addition of PVP-VA and sodium DNA compared to those treated with a placebo gel. 2019-004976-20.