Casein glycomacropeptide (CGMP) is a bioactive milk-derived peptide with potential anti-inflammatory effects. Animal studies suggest that CGMP may work by altering gut microbiota composition and enhancing butyrate production. Its effects on intestinal homeostasis, microbiota and metabolites in humans are unknown. The aim of the present study was to assess both the intestinal and systemic immunomodulatory effects of orally ingested CGMP. We hypothesised that a daily oral CGMP intake would reduce high-sensitive C-reactive protein in healthy adults. In a single-centre limited but randomised, double-blinded, reference-controlled study, we compared the effects of a four-week intervention of either 25 grams of oral powder-based chocolate-flavoured CGMP or a reference drink. We included twenty-four healthy adults who all completed the study. CGMP had no systemic or intestinal immunomodulatory effects compared with a reference drink, either with regard to high-sensitive C-reactive protein, or faecal calprotectin level, faecal microbiota composition or faecal short-chain fatty acid content. CGMP ingestion did not affect satiety or body weight, and it caused no severe adverse events. The palatability of CGMP was acceptable and adherence was high. CGMP did not induce or change gastrointestinal symptoms. In conclusion, we found no immunomodulatory effects of CGMP in healthy adults. In a minor group of healthy adults, oral ingestion of 25 grams of CGMP during four weeks was safe, well tolerated, had acceptable palatability, and was without any effects on body weight.