Objective: To systematically review the efficacy of laser photobiomodulation in reduction of pain induced during orthodontic treatment in human participants. Method: An extensive electronic search for randomized controlled trials and clinical controlled trials through Medline (PubMed), The Cochrane Controlled Clinical Trials Register and Science Direct till 30/12/2020 was done. Hand searching was performed for relevant journals. Reference articles were retrieved and exported to Mendeley Desktop 1.13.3 software. Risk of bias of included studies was assessed using the Cochrane risk of bias assessment tool. Articles were further analyzed using Revman 5.3 software. Forty-one articles were selected for review out of 175 retrieved articles. Results: Around 85% of the articles indicated laser photobiomodulation to be an effective modality in reduction of pain induced during orthodontic treatment. Risk of bias assessment revealed 6 articles with high risk of bias, 33 articles with unclear risk and 2 with low risk. Conclusion: Laser photobiomodulation can be a promising modality in reducing pain induced during orthodontic treatment.