William McKendree Gwin (October 9, 1805 – September 3, 1885) was an American medical doctor and politician who served in elected office in Mississippi and California.

William Gwin pursued classical studies and graduated from the medical department of Transylvania University in Lexington, Kentucky, in 1828.

As the son of a chaplain who was at the Battle of New Orleans, the young Gwin served as a personal secretary to President Andrew Jackson during the latter's second term.

Declining a renomination for Congress on account of financial embarrassment, he was appointed, on the accession of James K. Polk to the Presidency, to superintend the building of the new custom-house at New Orleans, Louisiana.

Gwin had a duel with Representative Joseph McCorkle with rifles at thirty yards following an argument over his alleged mismanagement of federal patronage.

In 1858, Gwin challenged Massachusetts Senator Henry Wilson to a duel, but they resolved their differences through a senatorial arbitration committee.

Gwin returned east to New York on the same ship as Edwin Vose Sumner, commander of the Union Army's Department of the Pacific.

However, President Abraham Lincoln intervened for their release, wishing to avoid an international incident, as Gwin had friends in Panama.

In 1864, he attempted to interest Napoleon III in a project to settle American slave owners in Sonora, Mexico.

Sheridan granted his original request for release to rejoin his family, which had also returned, but was countermanded by President Andrew Johnson.