Introduction Low-level laser therapy (LLLT) has a beneficial effect on pain relief and wound healing. This study aims at a clinical evaluation of early wound healing and a biochemical evaluation of inflammatory mediators in gingival crevicular fluid (GCF) following LLLT with an open flap debridement (OFD) in periodontal therapy. Material and methods This randomized controlled trial included 40 chronic periodontitis patients with bilateral attachment loss, pocket depths of 5 mm affecting at least two quadrants, and radiographic evidence of horizontal bone loss. 120 control sites were randomly selected to receive OFD, and contralateral 120 test sites received bio-stimulation with a diode laser (890 nm) after OFD. The wound healing index was recorded at the 1st and 2nd weeks, and clinical parameters such as the plaque index, gingival index, pocket probing depth, clinical attachment level, and GCF inflammatory mediators were evaluated at baseline, 3, and 6 months. Results From the start of the study to 6 months later, there was a statistically significant drop in plaque index, gingival index, probing pocket depth, and gain clinical attachment levels in both groups. However, when the two groups were compared, there were no significant differences at any time intervals. GCF inflammatory mediators tumor necrosis factor (TNF) alpha and matrix metalloproteinases (MMP-8) decrease, and osteoprotegerin (OPG) levels increase in both the test group and control group from baseline to 3 months and 6 months. In intergroup comparisons, there was a statistically significant reduction in the test group as compared to the control group at 6 months. There was a decline in gingival crevicular fluid - interleukin-6 (GCF IL-6) levels from baseline to 3 months and 6 months in both the groups but when analysed statistically, the results were not significant on intergroup and intragroup comparison at any time interval. The Landry Wound Healing Index values in the 1st and 2nd weeks were showing statistically significant improved healing in the test group as compared to the control group. There was significantly better wound healing at sites where a diode laser was used. Conclusion LLLT increases early wound healing after periodontal surgical procedures.