It has anti-inflammatory, anti-pyretic (fever reducing) and pain relieving qualities.

Like all NSAIDs, diflunisal acts by inhibiting the production of prostaglandins,^[2] hormones which are involved in inflammation and pain. Diflunisal also has an antipyretic effect, but this is not a recommended use of the drug. Though diflunisal has an onset time of 1 hour, and maximum analgesia at 2 to 3 hours, the plasma levels of diflunisal will not be steady until repeated doses are taken.^{[citation needed]} The long plasma half-life is a distinctive feature of diflunisal in comparison to similar drugs. To increase the rate at which the diflunisal plasma levels become steady, a loading dose is usually used. It is primarily used to treat symptoms of arthritis, and for acute pain following oral surgery, especially removal of wisdom teeth.

Effectiveness of diflunisal is similar to other NSAIDs, but the duration of action is twelve hours or more.^[3] This means fewer doses per day are required for chronic administration. In acute use, it is popular in dentistry when a single dose after oral surgery can maintain analgesia until the patient is asleep that night.