The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) reports that approximately 60–70 million people are affected by a plethora of chronic digestive disorders and problems, including irritable bowel syndrome, bloating and gas, constipation, diarrhea, lactose intolerance, fecal incontinence, acid reflux, Crohn’s disease, celiac disease, diverticulosis, and diverticulitis. Some of these diseases are short-term, while others are chronic and long-term. The digestive system comprises the gastrointestinal (GI) tract, liver, pancreas, and gallbladder, all of which function synergistically to digest food into essential nutrients for growth, energy, and cellular and metabolic homeostasis. Thus a healthy gut microbiome is vital for boosting immune competence and antiinflammatory conditions. A healthy functional diet is important to boost digestive function and health as well as immune competence by enhancing a healthy gut microbiome. An array of nutraceuticals and functional foods, including botanical extracts, structurally diverse digestive enzymes, probiotics, prebiotics, psychobiotics, and synbiotics, are beneficial for achieving and maintaining a healthy microbiome. This chapter provides fresh insight into the etiology of dysbiosis and digestive pathologies and discusses the strategic means for restoring a healthy GI ecosystem, promoting anti-inflammatory effects, preventing dysbiosis, and establishing optimal homeostatic equilibrium. Digestive metabolism and the roles of antioxidants, a healthy diet, standardized nutraceuticals, and epigenetic influences in improving systems’ biological synergies and maintaining an ideal ratio of Bacteroidetes to Firmicutes, and restoration of a healthy gut microbiome are also discussed with an emphasis on a systems biology perspective.