Background: Clerodendrum infortunatum is a medicinal plant found especially in the Sub-Himalayan regions of West Bengal. Various tribal communities of this region have been using these plants as a source of natural medicine. Objective: Medicinal values of C. infortunatum are well established, but the immunomodulatory properties have never been studied. Therefore, we wanted to investigate various immunomodulatory activities of this plant. Materials and Methods: Several parameters such as plaque-forming cell assay, hemagglutination titer, phagocytic activity of macrophages, and inhibition of lipopolysaccharide (LPS) were performed. Moreover, effects of C. infortunatum on the weight of various organs and total serum protein, albumin, and globulin levels were also determined. The phytochemical fingerprints of C. infortunatum extracts were obtained from Fourier transform infrared and gas chromatography-mass spectrometry analysis. Results: The macrophage stimulation and plaque-forming cell numbers (using sheep red blood cell as antigen) were significantly proliferated and found optimum at 100 and 250 mg/kg doses of leaf and root extracts simultaneously. The extent of stimulation in mural humoral immunity was in the order of leaf > root > stem. The anti-inflammatory activity of C. infortunatum was confirmed by the inhibition of LPS-induced nitric oxide synthesis by macrophages. Conclusion: It can be concluded that 70% hydromethanolic extract of C. infortunatum has profound immunomodulation potentials in the murine model, stimulating both humoral and innate form of the immune system.