Following his graduation De Pietro worked as a lawyer until 1915.{{cite web|title=De Pietro, Michele In 1942 De Pietro was arrested because of his anti-Fascist activities. In 1945 he was appointed member of the
National Council. He left the PLI in 1946 and later joined the
Christian Democrats (DC). In the elections on 18 April 1948 he was elected to the Italian Senate from the DC representing Lecce. In the 1953 elections he was again elected to the Senate and became vice president of the Senate which he held until 18 January 1954 when he was appointed minister of grace and justice to the first
cabinet led by
Prime Minister Amintore Fanfani. Although the cabinet's term ended soon, De Pietro continued to serve in the post in the subsequent
cabinet led by
Mario Scelba from 10 February 1954 to 6 July 1955. On 4 July 1957 De Pietro was again elected vice president of the Senate. Following the end of his tenure in 1958 he became president of the order of lawyers and prosecutors at the Court of Appeal and the Court of Lecce. Between 1958 and 1967 he was also president of the National Center for Prevention and Social Defense, succeeding
Alessandro Casati and
Enrico De Nicola in this position. ==Personal life and death==