Synthetic peptides containing three to six amino acid residues were previously shown to improve key parameters of monoclonal antibody-producing mouse hybridoma cultures. The aim of the current work was to investigate whether small peptides also exert analogous beneficial impact on a CHO-K1-derived cell line (XMK-111-10) engineered for production of the human model glycoprotein SEAP (secreted alkaline phosphatase). Similar to hybridoma cultures, growth and SEAP production profiles of CHO XMK-111-10 were modulated by peptides. Both viable cell density and SEAP production were increased by tetraalanine or by a fraction of wheat gluten hydrolysate. Whereas tetraglycine increased the peak viable cell density, the growth-suppressing tripeptide Gly-Lys-Gly significantly boosted SEAP production. All peptide-supplemented cultures showed slight improvement of culture viability during the decline phase of the batch cultures, suggesting a survival factor-like activity of the peptides.