Abstract The immune system is an essential defense against malignancy; immunosuppression increases the risk of developing cancer. A better understanding of how to modulate the immune system may lead to new methods to prevent and treat disease. While recent developments in targeted immunomodulation have improved cancer treatments, most therapeutics are toxic, expensive, or have marginal efficacy. We developed a natural product derived from fermented wheat germ extract (FWGE) that acts as an immune modulator. Through further purification we identified protein components, (fermented wheat germ proteins, FWGP), that are more potent than FWGE. In vitro, FWGP was cytotoxic against B cancer cells with IC50s ranging from 10μg/ml to 17.5μg/ml. In vivo studies showed substantial efficacy without toxicity. We found that FWGP was a potent immune modulator. It increased CD4+ T cells, NK-T cells, & activated monocytes by 4, 10, & 50 folds, respectively, while decreasing CD8+ T cells. CD56-bright NK cells treated with FWGP increased compared to the heat-inactivated FWGP treatment, and NK-mediated IFN-γ production rose as FWGP increased. Also, FWGP (0.1 mg/ml) activated complement with 2-fold potency compared to either control or FWGE (55mg/ml). It enhanced ADCC as well; PBMCs treated with FWGP showed a dose dependent increase in killing of Ramos. FWGP’s in vivo efficacy could be due to its immune modulating effects and may be the basis for a non-toxic treatment for lymphoma and other malignancies.