Drugs acting on opioid receptors remain the gold standard for pain control when acting centrally, and antidiarrheal when acting in the periphery. However, opioid use is limited by unwanted side effects including respiratory depression, abuse, and opioid-induced bowel dysfunctions. This thesis focuses on gut related disorders where the cells of the gut wall naturally release the natural opioids in small amounts but are increased under extreme and inflamed conditions. We are designing novel compounds to enhance the body’s natural gastrointestinal system response to treat diarrhoea without causing constipation.