Adjunctive use of laser devices as high reactive-level laser/light therapy (HLLT) or photobiomodulation therapy (PBMT) for periodontal therapy is known to be more effective on suppressing pain than conventional therapy, however, there are no systematic reviews addressed its effectiveness. This systematic review and meta-analysis aim to investigate the following clinical question (CQ): does adjunctive use of lasers with conventional therapy suppress the pain associated with periodontal treatment? A systematic and extensive literature search was performed to summarize the currently available knowledge to answer the CQ using the PubMed, Cochrane Library, and Web of Science databases for randomized controlled trials (RCTs) conducted before June 2020. Bias risk was assessed using the Cochrane tool for the risk of bias evaluation. A meta-analysis was performed on quantitative evaluation of pain control based on patient-reported outcomes. After an independent screening of 165 initial records, ten RCTs were included. Six of them focused on surgical procedures and the others on non-surgical periodontal pocket therapy. The protocols of HLLT, PBMT, and combination with HLLT and PBMT were employed in five, four and one RCTs, respectively. Following the assessment of bias risk, it is revealed that all RCTs had methodological weaknesses regarding the blinding of key personnel, although other bias risk factors were not evident. Meta-analysis showed that HLLT using erbium lasers significantly reduced the patient-reported pain immediately after treatment (two RCTs, p < 0.0001), while PBMT using diode lasers significantly reduced pain 2-7 days after treatment (two RCTs, p < 0.0001 to p = 0.03). The presented systematic review and meta-analysis suggest that the alternative use of HLLT using erbium lasers to conventional instrumentation can significantly suppress postoperative pain and that intraoperative or postoperative PBMT using diode lasers combined with periodontal surgery can significantly reduce postoperative pain. However, the evidence is still insufficient and more well-designed RCTs are required.