The Mandrake Root is originally set in Florence, Italy in 1504. The film relocates the action to Sassari in Sardinia in a similar period. The action takes place in the span of 24 hours and the comedy's main theme is the use of fraud, as none of the characters' objectives could be accomplished without it. Machiavelli makes it clear that fraud is acceptable, so long as it furthers a worthwhile cause and the plot revolves around which character is shrewder than the next.—Malachi Bogdanov

Callimaco, a young Sardinian returns from studying in Paris and is overcome by the beauty of Lucrezia, the virtuous and beautiful wife of the rich and foolish lawyer Nicia. In his desire to bed her, he engages the services of a dubious fixer Liguro who knows that Nicia and Lucrezia are desperate for a child. With Ligurio's help, Callimaco masquerading as a doctor, convinces Nicia that the surest way for his wife to conceive is by taking a potion made from the Mandrake Root, with the dire warning that the first man to sleep with her will die within 8 days. Nicia agrees to a plan to kidnap an unsuspecting man to sleep with his wife and thereby draw out the poison, but of course it is the disguised Callimaco who is to be kidnapped.—Malachi Bogdanov