The name Ysidro is of Spanish origin, derived from the Latin name Isidorus, which itself comes from the Greek name Isidoros, meaning "gift of Isis". The name Isis refers to the ancient Egyptian goddess of fertility and motherhood.

The name Isidorus was commonly used in the early Christian era, particularly among Hispano-Romans living in the Iberian Peninsula during the 6th and 7th centuries. One of the most famous bearers of this name was Saint Isidore of Seville, a renowned scholar and Archbishop of Seville, who lived from around 560 to 636 AD. He is known for his encyclopedic work, the Etymologiae, which was an influential compendium of knowledge in the Middle Ages.

Another notable figure with this name was Isidore of Miletus, a 6th-century Byzantine architect and mathematician, best known for designing the Hagia Sophia, the famous church in Constantinople (modern-day Istanbul). He lived from around 490 to 580 AD.

In the 9th century, the name Isidorus was anglicized to Isidore and became more common in parts of Western Europe. One example is Saint Isidore the Farmer, a Spanish day laborer and patron saint of farmers, who lived from around 1070 to 1130 AD.

The spelling variation Ysidro emerged in the medieval period, particularly in the Iberian Peninsula. One of the earliest recorded examples is Ysidro de Sevilla, a 13th-century Spanish prelate and Archbishop of Santiago de Compostela, who lived from around 1205 to 1278 AD.

Another notable figure was Ysidro Arredondo, a 16th-century Spanish conquistador and explorer, who participated in the conquest of Mexico under Hernán Cortés. He lived from around 1490 to 1555 AD.