Rheumatoid Arthritis (RA) is an autoimmune disease. The aim of this study was to investigate the effect of ginger supplementation on the expression of some immunity and inflammation intermediate genes in patients who suffer from RA. In this randomized double-blind placebo-controlled clinical trial, seventy active RA patients were allocated randomly into two groups who either received 1500 mg ginger powder or placebo daily for 12 weeks. Disease activity score and gene expression of NF-κB, PPAR-γ, FoxP3, T-bet, GATA-3, and RORγt as immunity and inflammation intermediate factors were measured using quantitative real-time PCR before and after the intervention. After the intervention, FoxP3 genes expression increased significantly within ginger group and between the two groups (P-value = 0.02). Besides, T-bet and RORγt genes expression decreased significantly between the two groups (P-value < 0.05). In ginger group, PPAR-γ genes expression increased significantly (P-value = 0.047) but the difference between the two groups wasn't statistically significant (P-value = 0.12). The reduction in disease activity score was statistically significant within ginger group and between the two groups after the intervention. It seems that ginger can improve RA by decreasing disease manifestations via increasing FoxP3 genes expression and by decreasing RORγt and T-bet genes expression. Display omitted •In the current study, after the intervention the FoxP3 genes expression increased significantly within ginger group and between the two groups (P-value= 0.02).•Besides, T-bet and RORγt genes expression decreased significantly between the two groups (P-value <0.05).•In ginger group, PPAR-γ genes expression increased significantly (P-value = 0.047) but the difference between the two groups was not statistically significant (P-value = 0.12).•The reduction in disease activity score was statistically significant within ginger group and between the two groups after the intervention.