Objectives: The aim of this study was to compare the clinical effects, presence of inflammatory cytokines, and the patients' perceived discomfort of two mechanical non-surgical methods of peri-implant maintenance: the piezo ultrasonic scaler vs hand instrumentation. Material and Methods: A total of thirty-four (34) patients with at least one healthy or with peri-implant mucositis dental implant were randomly assigned to the piezo ultrasonic scaler or to the hand instrumentation groups. The clinical parameters analyzed at the implant level were the following: Plaque Index (Pl), Bleeding on Probing (BOP), Probing Depths (PD), Keratinized tissue (KT) and Recession (REC). All these measurements were recorded at baseline, three, and six months. Full mouth plaque index (FPI) and full mouth bleeding on probing (FBOP) were also calculated. Samples of Peri-Implant Crevicular Fluid (PICF) from the four aspects of the implant were collected for analysis of cytokine levels followed by the corresponding maintenance therapy. At the end of the study patients were asked to fill in a pain questionnaire (Visual analogue scale, VAS). Results: Thirty-one (31) subjects completed the study (Piezo=17, SRP=14). Even though, reduction on FPI and FBOP were observed, it was found that the FPI and FBOP did not have a statistically significant difference over the 6 months or at any of the checkup times (0, 3, 6 months) for any of the treatment groups. Both peri-implant therapies slightly reduced the implant plaque index and implant probing depths in healthy and peri-implant mucositis implants from O to 6 months; however, these differences were not statistically significant. The model results indicated that the presence of KT and REC were not statistically significant different between treatments at any given time. This study demonstrated that the anti-inflammatory cytokine IL-4 statistically significant increased for both therapies from baseline to 6 months (P<0.05). There were not statistically association between the implant PD, Pl, and BOP and the cytokines levels (IL-2, IL-4, IL-6, ILB, IL-10, TNFa, and IFNy) during the six-month study period. In addition, subjects from both therapies reported minimum perceived discomfort after treatment. Conclusion: Within the limits of this study, it was demonstrated that both peri-implant therapies had a beneficial clinical effect in the reduction of all clinical parameters; however, these results were not statistically significant. In addition, there was no statistically significant difference in the clinical outcomes measurements at any given time between the two groups and the study could not demonstrated that peri-implant therapy decreases the presence of inflammatory cytokines.