Background: Orthodontically induced inflammatory root resorption (OIIRR) remains one of the most significant adverse effects of orthodontic treatment, potentially compromising long-term tooth stability. Photo biomodulation (PBM), delivered through low-level laser or light-emitting diode (LED) therapy, has emerged as a biological adjunct proposed to mitigate this phenomenon by modulating cellular metabolism and promoting tissue repair. Objectives: This systematic review aimed to evaluate the effectiveness of PBM in reducing orthodontic root resorption in human subjects undergoing fixed orthodontic treatment. Methods: An electronic search was conducted in PubMed, ScienceDirect, and the Cochrane Library for randomized controlled clinical trials published between January 2017 and October 2023. Studies were included if they compared PBM-assisted orthodontic treatment with conventional or placebo protocols and quantitatively assessed root resorption crater volume using three-dimensional imaging. Risk of bias was assessed using the Cochrane RoB 2 tool, and the overall quality of evidence was evaluated through the GRADE system. Results: Five randomized controlled trials met the inclusion criteria, comprising a total of 184 participants. Two studies demonstrated a statistically significant reduction in root resorption following PBM application, while three reported no significant difference compared with controls. No adverse effects were observed. The quality of evidence was graded as moderate due to interstudy variability in irradiation parameters, wavelengths, and energy doses. Conclusions: PBM shows promising potential as a safe, non-invasive adjunct to limit orthodontically induced root resorption. However, the heterogeneity of existing protocols precludes definitive clinical recommendations. Standardized, high-quality randomized trials are needed to determine optimal dosimetry and confirm PBM’s preventive and reparative role in OIIRR management.