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 painter
Jorge Juan Crespo de la Serna (1887–1978), Mexican artist, art critic and art historian
José de la Serna e Hinojosa (1770–1832), Spanish general and Viceroy of Peru
Juan Pérez de la Serna (1570–1631), seventh Archbishop of Mexico
Pedro Gómez de la Serna (1806–1871), Spanish jurist and politician
Ramón Gómez de la Serna (1888–1963), Spanish writer
Rodrigo de la Serna (born 1976), Argentine actor
