John Isaac Guion (November 18, 1802 – June 6, 1855) was an American politician from Mississippi who served as Governor in 1851.

He studied law in Lebanon, Tennessee, was admitted to the bar, and established a successful practice in Vicksburg, Mississippi.

In February 1851, Governor John A. Quitman resigned to defend himself against charges of aiding in filibustering expeditions against Spanish rule in Cuba.

Guion became acting governor and served until November when his Senate term expired.

Since no one in the line of succession could assume the governorship, the legislature subsequently chose James Whitfield as an interim replacement, and he served until the term of the new governor started in 1852.