Collagen is a major extracellular matrix protein. Given the potential anti-inflammatory and antioxidant

profiles of these bioactive compounds, there has been increasing interest in using collagen derived peptides

and peptide-rich collagen hydrolysates for skin health, due to their immunomodulatory, antioxidant

and proliferative effects on dermal fibroblasts. However, all hydrolysates are not equally effective in exerting

the beneficial effects; hence, further research is needed to determine the factors that improve the

therapeutic applicability of such preparations.Weused different enzymatic conditions to generate anumber

of different collagen hydrolysates with distinct peptide profiles. We found that the use of two rather

than one enzyme for hydrolysis generates a greater abundance of low molecular weight peptides with

consequent improvement in bioactive properties. Testing these hydrolysates on human dermal fibroblasts

showed distinct actions on inflammatory changes, oxidative stress, type I collagen synthesis and

cellular proliferation. Our findings suggest that different enzymatic conditions affect the peptide profile

of hydrolysates and differentially regulate their biological activities and potential protective responses

on dermal fibroblasts.