Its active ingredients are diphenoxylate and atropine. Diphenoxylate is anti-diarrheal and atropine is anticholinergic. Diphenoxylate is chemically related to the opioid drug meperidine. A subtherapeutic amount of atropine sulfate is present to discourage deliberate overdosage. Atropine has no anti-diarrheal properties, but will cause tachycardia when overused. The medication diphenoxylate works by slowing down the movement of the intestines.

The inactive ingredients of Lomotil (as a liquid; it comes in pill form as well) are cherry flavor, citric acid, ethyl alcohol 15%, FD&C Yellow No. 6, glycerin, sodium phosphate, sorbitol, and water.

Other trade names for the same therapeutic combination are Lofene, Logen, Lomanate and Lonox, among others. In other countries, Lomotil may have other names.

Diphenoxylate (R-1132) is an opioid agonist used for the treatment of diarrhea that acts by slowing intestinal contractions and peristalsis allowing the body to consolidate intestinal contents and prolong transit time, thus allowing the intestines to draw moisture out of them at a normal or higher rate and therefore stop the formation of loose and liquid stools. It is the main active ingredient in the anti-peristaltic medication Lomotil, which also contains atropine as noted below.

Diphenoxylate is the prototype of a small subfamily of opioids including difenoxin and diphenoxylic acid (both are also active metabolites of diphenoxylate produced in the human body) and loperamide (which unlike the other three work exclusively in the intestines because it does not cross the blood-brain barrier). It was discovered at Janssen Pharmaceutica in 1956. It is a congener to the narcotic pethidine of which the common brand names are Dolantin and Demerol amongst others. Other somewhat more distant relatives include alphaprodine (Nisentil) and piritramide (Dipidolor).