CD80 expression was highest in the Melatonin group and lowest in the Thymoquinone group (p=0.000), while CD206 expression was highest in the Bromelain group and lowest in the Thymoquinone group (p=0.00).<h4>Conclusion</h4>Thymoquinone exhibited comparatively more favorable patterns, and overall, all agents showed trends that may support their consideration as adjunctive approaches in periodontitis management. This evidence concerns the gene CD80 and periodontitis.