Periodontitis is a chronic inflammatory disease of the tooth-supporting structures, often causing alveolar bone loss due to increased osteoclast activity mediated by receptor activator of nuclear factor-kappa B ligand. Curcumin is believed to have immunomodulatory effects and has been proposed as a natural therapeutic agent targeting receptor activators of nuclear factor-kappa B ligand expression. This study aims to evaluate and review the immunomodulatory effects of curcumin on receptor activators of nuclear factor-kappa B ligands in periodontitis. This systematic review followed the PRISMA 2020 guidelines. A search of published literature in PubMed, Scopus, ScienceDirect, and Google Scholar was employed. Risk of bias assessment was performed using three different tools, including QUIN for in vitro studies, SYRCLE’s RoB for animal model studies, and Cochrane RoB 2 for clinical trials. All studies evaluating curcumin’s effects on receptor activator of nuclear factor-kappa B ligand levels, both membrane receptor activator of nuclear factor-kappa B ligand and soluble receptor activator of nuclear factor-kappa B ligand, were considered for inclusion in this review. Of the 307 potentially eligible studies, four studies were ultimately retrieved. This study found that there is a significant decrease in receptor activator of nuclear factor-kappa B ligand levels after curcumin administration. The immunomodulatory effects of curcumin are believed to be through modulation of macrophage polarization and inhibition of the nuclear factor kappa-B signaling pathway, and possibly indirectly through inhibition of autophagy. Thus, curcumin shows promising potential as an adjunct agent for periodontitis through the mechanism of decreasing receptor activator of nuclear factor-kappa B ligand levels which then reduces alveolar bone loss. Large-scale clinical trials with rigorous methods are warranted to determine the optimal dosage, formulation, and long-term safety for clinical application in periodontal therapy targeting receptor activators of nuclear factor-kappa B ligand.