Thyroid and parathyroid surgery are considered clean procedures, with an incidence of surgical site infection (SSI) after thyroidectomy ranging from 0.09% to 2.9%. International guidelines do not recommend routine antibiotic prophylaxis (AP), while AP seems to be employed commonly in clinical practice. The purpose of this systematic review is analyzing whether the postoperative SSI rate in thyroid and parathyroid surgery is altered by the practice of AP. We searched Pubmed, Scopus, the Cochrane Library, and Web of Science (WOS) for studies comparing AP to no preoperative antibiotics up to October 2021. Data on the SSI rate was evaluated and summarized as relative risks (RR) with 95% confidence intervals (95% CI). Risk of bias of studies were assessed with standard methods. Nine studies (4 RCTs and 5 nRCTs), including 8710 participants, were eligible for quantitative analysis. A meta-analysis showed that the SSI rate was not significantly different between AP and no preoperative antibiotics (SSI rate: 0.6% in AP vs. 2.4% in control group; RR 0.69, 0.43-1.10 95% CI, = 0.13, I2 = 0%). A sensitivity analysis and subgroup analysis on RCTs were consistent with the main findings. Evidence of low quality supports that AP in thyroid and parathyroid surgery produce similar SSI rates as to the absence of perioperative antibiotics.