In the religion of Islam, he is regarded as the final prophet of God (Allah in Arabic, or El in Hebrew).
A descendant of Abraham, Muhammad was a social reformer, diplomat, merchant, philosopher, orator, legislator, military leader, humanitarian, and philanthropist. After unifying the Arabian Peninsula during his lifetime, his followers went on to establish the Islamic Caliphate (also known as the Arab Empire), which at its height stretched from India in the east to Spain in the west (larger than the Roman Empire and Persian Empire combined), eventually coming to an end with the Ottoman Empire's fall in the 1920's. In his book of the 100 most influential people, Michael H. Hart ranked Muhammad as the most influential man in history.
Depicting his visage is considered taboo in Islam, the reasoning being to prevent him from becoming worshipped like Jesus. As a result, various controversies have arisen upon his appearance in modern art. When he is depicted, his face is often either censored or not shown at all.
The earliest reference to Muhammad in video games is in the Japanese action role-playing game XZR, which in the opening describes an overview of his foundation of Islam and the subsequent history of Islam, before beginning the main story centuries later.
Muhammad is also indirectly referenced in the backstory of the Dune franchise of sci-fi novels, films, games, and shows, within the history of the Fremen people, nomadic desert dwellers of the planet Arrakis (a.k.a. Dune) who more or less follow a future variant of Islam. The protagonist Paul Atreides' role as Muad'Dib to the Fremen people also parallels Muhammad's role as Prophet to that of the Bedouin Arabs.
In Chrono Trigger, certain aspects of Magus' character appears to parallel the Islamic prophet Muhammad, both of whom founded a religion in the early 600's and established religious states in a city called 'Medina'. The conflict between the Mystics and Guardians also appears to parallel the Muslim-Christian conflicts of the Middle Ages, such as the Arab-Byzantine Wars (600's-700's) and the Crusades (1100's-1300's).
Modern depictions of Muhammad in video games include a negative depiction in Muslim Massacre: The Game of Modern Religious Genocide, as a boss character (after the player has carried out a genocide against Muslims, that is), and a more neutral depiction in the Faith Fighter series of fighting games, which gives players the option of whether or not to censor his face.