This systematic review aimed to investigate the influence of periodontitis on post-transplant IL-6 serum levels of solid organ transplanted patients as compared to healthy subjects. Four databases (PubMed, Scholar, EMBASE, and CENTRAL) were searched up to February 2020 (PROSPERO CRD42018107817). Case-control and cohort studies on the association of IL-6 serum levels with a periodontal status of patients after solid organ transplantation were included. The risk of bias of observational studies was assessed through the Newcastle-Ottawa Scale (NOS). Random effects meta-analyses were thoroughly conducted. GRADE assessment provided quality evidence. Four case-control studies fulfilled the inclusion criteria (274 transplant recipients and 146 healthy controls), all of low risk of bias. Meta-analyses revealed significantly higher IL-6 levels in transplanted patients than healthy individuals with low-quality evidence (Mean Difference (MD): 2.55 (95% confidence interval (CI): 2.07, 3.03)). Transplanted patients with periodontitis have higher serum IL-6 levels than transplanted patients without periodontitis with moderate quality evidence (MD: 2.20 (95% CI: 1.00, 3.39)). We found low-quality evidence of higher IL-6 levels than healthy patients in patients with heart and kidney transplant. In these transplanted patients, there was moderate quality evidence that periodontitis is associated with higher IL-6 serum levels. Future research should consider the impact of such a difference in organ failure and systemic complications.