The clinical effectiveness of the erbium-doped yttrium-aluminum-garnet (Er:YAG) laser in patients with peri-implantitis remains unclear. The aim of this meta-analysis was to investigate the efficacy and safety of Er:YAG laser (ERL) compared to subgingival mechanical debridement (SMD) for the treatment of peri-implantitis. A systematic electronic literature search was conducted to identify randomized clinical trials (RCTs), followed by a manual search. Results were expressed as weighted mean differences (WMDs) with accompanying 95 % confidence intervals (CIs). The primary outcome measurements were changes in clinical attachment level (CAL) and probing depth (PD). Secondary outcome measurements included changes in gingival recession (GR). The meta-analysis was performed with fixed-effect or random-effect model according to the heterogeneity assessed by I (2) test. Visual asymmetry inspection of the funnel plot, Egger's regression test, and the trim-and-fill method were used to investigate publication bias. At 6 months, significant difference in PD reduction (p = 0.018) was observed for Er:YAG laser compared to SMD treatment, while no significant differences were detected in CAL gain and GR change; at 12 months, no significant difference was observed for any investigated outcome. The findings of this meta-analysis suggest that use of the Er:YAG laser as alternative to SMD could potentially provide short-time additional benefits, while there is no evidence of long-time superior effectiveness. As all included studies were not at low risk of bias, and only four studies were included in the meta-analysis, future long-term and well-designed RCTs reporting clinical and microbiological outcomes, considering the cost/effectiveness ratio, and having a high methodological quality are needed to clarify the effectiveness of Er:YAG laser.