Galectins are animal lectins that bind glycoconjugates containing β-galactose proteins. Galectin (gal)-3 and gal-9 expressions have been associated with innate and adaptive immunity, and inflammation response. Plant-derived polyphenols found in feed have a beneficial effect on animal health. The objective of the study was to determine the effect of polyphenol extract from cowpea (CPE) on gal-3 and gal-9 mRNA levels and protein expression in bovine peripheral blood. Blood collected from Holstein cows (n = 10) was treated with 10μg of CPE, controls were treated with either 100 ng/mL of lipopolysaccharide (LPS), or left untreated. Total RNA was extracted after treatment; reverse transcribed to cDNA and real-time PCR was performed using specific primers for bovine gal-3 and gal-9. Real-time PCR data analysis normalization was performed with the housekeeping gene GAPDH and fold change (FC) in gene expression was calculated using the 2^−ΔΔCT method. Plasma concentration of gal-3 and gal-9 was measured using a commercial ELISA. One-way ANOVA was performed on gal_3 and gal_9 concentration data, a P-value of < 0.05 was considered significant. Results from the RT-PCR showed increased mRNA levels of gal_3 (FC = 48.90) and Gal_9 (FC = 147.41) after LPS treatment relative to the untreated controls. In the CPE-treated samples, the relative gene expression of gal-3 and gal-9 were 1.72 and 2.07 respectively. Also, the concentrations of gal-3 and 9 in plasma increased in LPS-treated samples but decreased in the CPE-treated group relative to the untreated control. The results from this study showed that polyphenols from cowpea modulate gal-3 and gal-9 mRNA and protein expression in bovine blood. Hence, the use of polyphenols extract from cowpea enriched feed supplements may have immunomodulatory properties for animal health, and aid in the design of galectin-based strategies to counteract LPS induced inflammation and morbidities.