He later studied law in Missouri and Kentucky, attained admission to the bar, and moved to Edwardsville, Illinois, to start a practice.

After leaving politics, Semple practiced law, was active in several business ventures, and attempted to market an invention called the prairie car, a forerunner of the modern automobile.

[1] In response to the Panic of 1819, Missouri's government authorized the issuing of paper money that could be loaned to farmers so that they wouldn't lose their land during the economic downturn.

[2] After the sudden death of his first wife in 1821, Semple decided on a career as an attorney and began to study law.

[1] He moved to Louisville, Kentucky, in 1824 to continue his studies, and after three years of learning he was admitted to the bar and returned to Edwardsville in 1827 to start a law practice.

[1] During the Black Hawk War of 1832, Semple was appointed adjutant of the Illinois Militia's 8th Infantry Regiment, then adjutant of a newly organized mounted regiment, and then aide-de-camp to Brigadier General Samuel Whiteside and judge advocate of Whiteside's brigade.

[1] In addition to practicing law, he became involved in business ventures including real estate speculation, and was one of the founders of the town of Highland and the villages of Tamaroa and Marine.

[1] As Chargé, Semple was empowered to act as a minister, and was commended by New Granada's government and members of the various groups opposed to it for the tact and fairness with which he advocated for U.S. interests without showing favoritism.

[1] On January 6, 1843, Semple was appointed an associate justice of the Illinois Supreme Court, filling the vacancy left when Sidney Breese resigned to accept election to the U.S.

[1] Consular appointments were patronage positions, and most incumbents received no salary, but were compensated by the fees they were allowed to charge for notarizing travel documents, verifying the passenger manifests of arriving U.S. ships, and verifying the contents of arriving U.S. cargo ships.

[4] Semple introduced a bill that would have professionalized the consular corps and provided for the payment of salaries in lieu of fees, but it was not adopted during his time in the Senate.

[1] Semple's prairie car was a wagon fitted with a steam engine and wide tires that enabled it to run on roads or rough terrain.

[1] He purchased an estate in Jersey County, where in 1853 he founded the town of Elsah, Illinois, and owned businesses including a mill and a distillery.

[1][3] During the American Civil War, Semple was sympathetic to the states' rights arguments of the Confederacy, but remained loyal to the Union and supported measures including loyalty oaths.