Alginates are versatile biopolymers used extensively in the food, textile and pharmaceutical industries. One of the major uses is in the treatment of reflux disease and here we investigate whether alginates can influence pepsin activity, a major aggressor in reflux disease. The primary uronic acid structure of alginates can be altered using epimerase technology and we test tailor-made alginates to identify the optimal structure for pepsin inhibition. Pepsin activity in the presence of alginates was studied using an in vitro N-terminal assay and enzyme kinetics using a chromagenic peptide. The data described showed clearly that alginates were capable of concentration dependently reducing the activity of pepsin in a non-competitive manner, in vitro. This was variable between different alginates of wide ranging structure and size with positive correlation with alternating sequences of mannuronic and guluronic acid. We hypothesize that alginates may have a more extensive role in the treatment of reflux disease by inhibiting pepsin, a damaging component of the refluxate.