Orally administered physiologically acceptable anti-biofilm compositions comprising enzymes and if desired additional components such as antimicrobials, antibiotics, antifungals, herbals, chelating agents, lactoferrin and related compounds, minerals, surfactants, binders, and fillers useful for the inhibition and treatment of gastrointestinal biofilms in humans. Physiologically acceptable anti-biofilm compositions containing these enzymes are useful in the inhibition, reduction and/or treatment of gastrointestinal biofilm infections, and associated systemic symptoms caused by biofilms associated microorganisms within the gastrointestinal tract. Methods of identification, preparation and use of such physiologically acceptable anti-biofilm compositions are also provided.