Bovine colostrum (BC) has been used for nutraceutical purposes for animals and humans. Bovine colostrum is a complex heterogeneous product and its antimicrobial activity, antioxidant potential, and growth factors can vary depending on age and species of the cow as well as their environment. Bovine colostrum preparation in skimmed or whey fractions can also alter properties of BC. Our goal was to compare cumulative anti-inflammatory, antioxidant, and adipogenic properties of natural (whole) versus whey BC. We compared properties of whole and whey BC in 3T3-L1 preadipocytes permanently transfected with reporters responding to changes in inflammatory (NfκbRE/green fluorescent protein), anti-inflammatory (Nrf2/YFP), and adipogenic (Fabp4/cyan fluorescent protein) status in cells. Interleukin-6 secretion in these cells was measured by ELISA. Whole and whey BC induce IL-6 secretion from 3T3-L1 fibroblasts; however, whey preparation stimulated less IL-6 secretion. Cumulative inflammatory nuclear factor (NF)κB activation in the presence of lipopolysaccharide was reduced by both whole (-27%) and whey BC (-22%) compared with lipopolysaccharide-treated cells (100%). Treatment with whole BC was more effective in the reduction of NFκB activation compared with whey BC and occurred in a dose-dependent manner. In consonance with decreased NFκB activation, the Nrf2 promoter activity was also reduced in response to whole (-27%) and whey (-13%) treatments compared with nontreated cells (100%). Whole and whey BC suppressed adipogenesis, measured as induction of Fabp4, by -27 and -13%, respectively, compared with nontreated 3T3-L1 fibroblasts (100%). Our results showed distinct differences in properties of whey and whole BC that could be used to attain reduced adipogenic or cumulative inflammatory responses.