The Second Federal Republic of Mexico (Spanish: Segunda República Federal de México) is the name given to the second attempt to achieve a federalist government in Mexico after a period of centralism. Officially called the United Mexican States (Estados Unidos Mexicanos), a federal republic was established again on August 22, 1846 when interim president José Mariano Salas issued a decree restoring the 1824 constitution. The Second Republic continued to be rocked by the political instability that had characterized Mexico since independence. Mexico's loss in the war with the United States during this time saw half of Mexican territory become part of the United States.

Antonio López de Santa Anna who had played a major role in the war, and been disgraced as a result, afterwards returned to the presidency, selling more territory to the United States and becoming increasingly autocratic. In response, liberals promulgated of the Plan of Ayutla in 1854, calling for the overthrow of Santa Anna's dictatorship. Santa Anna was overthrown and liberals enacted a series of sweeping reforms, including a new federalist constitution, collectively known as the Liberal Reform, which then sparked a civil war with conservatives, known as the War of the Reform, from 1857 to 1860. The conservatives lost the war, but the liberals' triumph however was soon interrupted by a French invasion in 1861, which gained collaboration from the recently defeated conservatives.

The French attempted to set up a client state known as the Second Mexican Empire. Conservatives invited Maximilian Habsburg to serve as monarch of the Empire. Mexican republicans nonetheless fought against the French invaders, led by Benito Juárez's government in exile, which was backed by the United States. Ultimately the French were unable to consolidate control of the entire nation and under pressure from the United States which after the end of the Civil War, could more effectively enforce the Monroe Doctrine, withdrew from Mexico, leading to the Empire's collapse in 1867.

The period of the Second Republic following the end of the Second Empire, is known as the Restored Republic.