Due to the presence of the cardiac glycoside digitoxin, the leaves, flowers and seeds of this plant are all poisonous to humans and some animals and can be fatal if ingested. The main toxins in Digitalis spp. are the two chemically similar cardiac glycosides: digitoxin and digoxin. Like other cardiac glycosides, these toxins exert their effects by inhibiting the ATPase activity of a complex of transmembrane proteins that form the sodium potassium ATPase pump, (Na+/K+-ATPase). Inhibition of the Na+/K+-ATPase in turn causes a rise not only in intracellular Na+, but also in calcium, which in turn results in increased force of myocardial muscle contractions. In other words, at precisely the right dosage, Digitalis toxin can cause the heart to beat more strongly. However, digitoxin, digoxin and several other cardiac glycosides, such as ouabain, have narrow therapeutic windows (i.e., because of their steep dose-response curves, minute increases in the dosage of these drugs can make the difference between an ineffective dose and a fatal one). There are now better options with a wider therapeutic window. Symptoms of Digitalis poisoning include a low pulse rate, nausea, vomiting, and uncoordinated contractions of different parts of the heart, leading to cardiac arrest and finally death.

Extracted from the leaves, this same cardiac glycoside digitoxin is used as a medication for heart failure. Its clinical use was pioneered by William Withering, who recognized it "reduced dropsy", increased urine flow, and had a powerful effect on the heart by making it beat slower but more efficiently waiting for the heart to fill with blood before pumping.