This study aimed to evaluate the efficacy of low-level laser application in the treatment of periodontal intra-bony defects. Two independent reviewers conducted searches for articles published in English. The primary objective was to investigate whether clinical parameters improved in periodontal regeneration therapy with and without low-level laser therapy (LLLT). The primary outcome was probing depth (PD), while the secondary outcome measures were clinical attachment level (CAL), gingival recession (GR), and bone defect depth. After screening and eligibility assessment, eight studies were included in the analysis. For the primary outcome measure (PD), after sensitivity analysis, the reduction in PD from baseline to 3 months was greater in the laser group than in the non-laser group (P = 0.02). For the secondary outcome measure (CAL), after sensitivity analysis, the increase in CAL from baseline to 3 months was greater in the laser group (P < 0.001). Although laser therapy may be beneficial for early wound healing, the current evidence does not support its routine use in periodontal regenerative surgery. Further high-quality studies are warranted to evaluate its clinical efficacy.