Background: In orthodontic treatment, mini-screws can provide maximum anchorage conditions. If the miniscrew stability is compromised, this could jeopardize the outcomes of the orthodontic treatment or biomechanics. Photobiomodulation therapy (PBMt) is beneficial for biological tissues since it promotes wound healing with its anti-inflammatory and osteo-stimulatory properties. Objectives: The purpose of this study was to evaluate the effects of 810-nm Diode PBMt on the stability of orthodontic mini-screws for three months. Trial Design: Parallel, allocation ratio 1:1. Methods: Using a split-mouth technique, a total of 40 mini-screws were randomly allocated (1:1) to either a placebo laser application (P group) or a laser PBMt (L group). An 810-nm diode laser irradiation of 1 W output power, operating in continuous wave mode for 50 s, was applied in a sweeping movement at a 22 mm distance from the mini-screws. The allocated mini-screws first received PBMt at baseline, then every other day for five days, and then at each orthodontic visit (every three weeks) for a period of three months. At each visit, the stability of the mini-screws was measured by the Osstell Implant Stability Quotient (Osstell ISQ) at three points: lower, upper, and distal to the mini-screw. Results: The lower, upper, and distal ISQ values of irradiated and non-irradiated mini-screws significantly decreased at each point over time (p < 0.001). No significant difference was found in the global ISQ values between the laser and the placebo group (p > 0.05). Conclusion: PBM did not significantly increase the stability of orthodontic mini-screws over a period of three months. Trial Registration: Protocol was approved by the Research Ethics Committee of the Faculty of Dental Medicine of Saint Joseph University, Beirut, Lebanon University (#USJ/2019/161).