de la Serna is a surname. Notable people with the name include:
Jacobo de la Serna (born 1965), American ceramic artist, Spanish Colonial scholar, and painterJorge Juan Crespo de la Serna (1887–1978), Mexican artist, art critic and art historianJosé de la Serna e Hinojosa (1770–1832), Spanish general and Viceroy of PeruJuan Pérez de la Serna (1570–1631), seventh Archbishop of MexicoPedro Gómez de la Serna (1806–1871), Spanish jurist and politicianRamón Gómez de la Serna (1888–1963), Spanish writerRodrigo de la Serna (born 1976), Argentine actor