This study examined the effect of curcumin on T-helper (Th17) and T-regulatory (Treg) cells regarding the mRNA of cytokines/mediators in the gingiva. Thirty-five male albino Wistar rats were divided into four groups: Group 1: periodontitis (n = 9): Group 2: periodontitis with curcumin treatment (n = 8): Group 3: periodontally healthy with curcumin treatment (n = 10); and Group 4: periodontally healthy (n = 8). Curcumin was administered via oral gavage (30 mg/kg/day) for a total of 15 days. The gingival tissues were investigated regarding mRNA expressions of Th17/Treg cytokines with qRT-PCR. The distributional properties of the data were evaluated using the Anderson-Darling normality test. Kruskal-Wallis and Mann-Whitney U tests were employed for multiple group comparisons. Partial least squares regression discriminant analysis (PLS-DA) was used to evaluate the degree of contribution of each mRNA to the separation of treatment groups. When the periodontitis groups were compared, curcumin treatment resulted in lower IL-1 beta (Group 2 median: 0.002, Group 1 median: 0.12) and IL-6 (Group 2 median: 0.031, Group 1 median: 0.078) and higher IL-17 (Group 2 median: 1.07, Group 1 median: 0.583) relative mRNA expression in Group 2 than in Group 1 (p < 0.001). Group 3 also had higher IL-10 relative expression (median: 0.067) than Groups 1 and 4 (median: 0.028, 0.007, respectively. p < 0.001). These results indicate that curcumin might be a promising agent for the prevention and/or treatment of periodontal diseases due to its decreasing effect on IL-1 beta and IL-6 mRNA expression.