Sant'Alessio was most likely built in the early fifth century on the site of one of the original house churches on the Aventine. The church is sometimes said to be dedicated to Saint Boniface as well as Saint Alexis. According to legend Saint Boniface was a Roman slave who had a sexual relationship with his mistress, then repented and went off on a crusade and was martyred in Turkey. Why he is associated with this site on the Aventine is unclear. Saint Alexis of Edessa was an Eastern Saint whose veneration was later transplanted to Rome. He lived in Mesopotamia as a beggar shared the alms he received with the poor. A legend developed after his death that he was a native of Rome and grew up on the Aventine Hill. His name was added the church's dedication by Pope Honorius III when devotion to him became popular. There is no evidence that either Saint had anything to do with the church named in their honor.
The earliest evidence for the existence of the church on this location comes from the Liber Pontificalis for Leo III (750-816 CE) where it is described as a diaconia or center for social and charitable works. The institution was later given to the Greek archbishop Sergius who established a monastery there for Latin and Byzantine monks. In the early 10th century when relations between Eastern and Western churches broke down, the Byzantine monks were replaced by Benedictines from Cluny Abbey. Later the Benedictines were replaced by Premonstratensians who were themselves replaced by the reformed Order of Hieronymites of Lombardy in 1426. When the Hieronymite monasteries were suppressed in 1835, the Somaschi Fathers were installed. They ran a school for blind children on the site, but rarely opened the church for services. In 1929 they lost their Roman headquarters at San Nicola dei Cesarini and moved to Sant’Allesio all’Aventino, where they remain today.
The church and monastery have a spectacular view over Trastevere in the direction of the Vatican. A boundary wall on the east side of the court separates the property of Sant'Allesio from Santa Sabina. The fourth bay of the aisle of Sant'Allesio has a chapel dedicated to of Saint Jerome and an 18th century altarpiece shows Saint Jerome with his student Saint Marcella. This mutually beneficial relationship is described in more detail in an earlier post about Saint Marcella. Sant'Allesio was most likely built on the site of the palace owned Saint Marcella's family in 325 CE. Saint Marcella's mother Albina bequeathed the estate to her daughter after her husband's death, and the two of them turned the palace into a monastery. Saint Marcella drew around her a community of widows who were consecrated to a life of prayer, fasting and the study of sacred texts.
The community lived in complete seclusion except for visits to the tombs of the martyrs nearby and contributed to the development of the monastic way of life. In 382 CE Jerome arrived in Rome and the Pope sent him to Marcella for lodging. The strict ascetic practices of the community led to the untimely death of a young member of the community in 383 CE. The girl’s relatives blamed Jerome for her death and forced him to leave Rome. Jerome fled to Egypt and Palestine with two members of the community, while Marcella remained in her home on the Aventine. In 410 CE the Visigoths attacked Rome. Marcella, by then an elderly year old widow, was beaten, tortured and driven out into the street. She took refuge in the Church of St. Paul, but died the next day when her monastery was pillaged and destroyed.