Previously we identified a sodium caseinate (NaCas) hydrolysate, LFC25, which significantly increased secretion of satiety hormone glucagon-like peptide-1 (GLP-1) in vitro and reduced food intake in mice when administered intraperitoneally. This study investigates whether LFC25, administered orally, promotes GLP-1 secretion and/or reduces food intake in vivo. Over an 8-hour period, mice received LFC25 by oral gavage had similar food intake to mice received NaCas. Postprandial blood glucose, plasma active GLP-1, amino acids, insulin and food consumed at the next meal were not significantly different in pigs that consumed LFC25 compared to NaCas in a dairy beverage, at a dosage relevant for human consumption. Simulated in vitro gastro-duodenal digestion of LFC25 revealed a significant reduction in bioactivity. In contrast, the harsh conditions of the upper gut appear to functionalize intact NaCas as a GLP-1 secretagogue. In conclusion, LFC25 will need enteric protection to be used as a food ingredient for satiety.