Background: Euphorbia plants are traditionally used in folk medicine for infections, inflammation, and cancer. Objectives: To investigate the effects of the butanolic extracts of Euphorbia micorociadia and Euphorbia osyridea on specific transcription factors and cytokines expression of T cell subsets. Methods: Activated mouse splenocytes were cultured in the presence of non-cytotoxic concentrations of the extracts. Cells were evaluated for the gene expressions of T cell transcription factors and cytokines of T helper (Th)1 [T-bet and interferon gamma (IFNγ)], Th17 [retinoic acid receptor related orphan receptor (RORγt) and interleukin (IL)-17], and T regulatory (Treg) cells [forkhead box P3(Foxp3), IL-10, and Transforming growth factor (TGF)-β] using real-time PCR. The cytokine secretions were evaluated by ELISA and Foxp3 protein expression by flow cytometry. Results: Both E. osyridea and E. microciadia extracts at 0.1 μg/ml increased T-bet expression [>1.73 relative fold change (RFC), p<0.05] and IFNγ production (>1195 pg/ml, p<0.001). Both decreased Foxp3 (<0.41 RFC, p<0.05) expression. At the higher concentration both extracts significantly reduced T-bet mRNA as well as IFNγ, IL-17, IL-10, and TGF-β cytokines and Foxp3 at the mRNA and protein levels. Conclusion: These data showed the immunomodulatory effects of E. osyridea and E. micorociadia extracts on T cell-mediated responses. The extracts caused upregulation of Th1 and downregulation of Treg cells at a low concentration which suggested their possible therapeutic value in tumor models and infectious diseases. The observed immunosuppressive effects at the higher concentration potentially make these plants candidates for identification of active components and studying their mechanisms of action.