Born in Wuerzburg, Germany. He came to Japan for the first time in 1823, as a resident physician at the Dutch East India Company Dejima Factory. He was allowed to open the Narutaki-Juku private school, and gave medical lectures to his pupils, thereby contributing to the development of Japanese medicine. During his stay, he also conducted academic investigations in such fields as Japanese history, religion, geography, folklore, and manners and customs.
Siebold needed precise specimen illustrations for his research, and required the Batavia's governor-general to dispatch painters. In response, de Villeneuve was dispatched to Dejima as a painter, and taught the basics of Western painting to Kawahara Keiga, who painted various objects in Japan in response to the requests of Siebold. After returning to his country, Siebold authored the great work “Nippon.”
In 1826 Siebold made the court journey to Edo. During this long trip he collected many plants and animals. But he also obtained from the court astronomer Takahashi Kageyasu several detailed maps of Japan and Korea (written by Ino Tadataka), an act strictly forbidden by the Japanese government. When the Japanese discovered, by accident, that von Siebold had mapped northern parts of Japan, the government accused him of high treason and of being a spy for Russia.
The Japanese ordered Siebold into house arrest and expelled him from Japan on October 22, 1829. Satisfied that his Japanese collaborators would continue his work, he journeyed back on the frigate Java to his former residence, Batavia, in possession of his enormous collection of thousands of animals and plants, his books and his maps. The botanical garden of Buitenzorg would soon house von Siebold's surviving, living flora collection of 2,000 plants. He arrived in the Netherlands on July 7, 1830. His stay in Japan and Batavia had lasted for a period of eight years.
As a well-known expert on Japan, Siebold discovered that his expertise and opinions were sought after by a range of questioners. Whilst living in Boppard, from 1852 he was became involved in correspondence with Russian diplomats such as Baron von Budberg-Bönninghausen, the Russian ambassador to Prussia. American Naval Commodore Matthew C. Perry consulted Siebold in advance of his voyage to Japan in 1854.
In later years, von Siebold became an adviser on Japanese cultural and social issues for several governments. This position granted Siebold a return to Japan as an "adviser" from 1859 till 1863. While back in Japan, he went to see Kusomoto Sonogi several times. His proposals for a "cultural" approach to the Japanese, instead of a "mercantile" approach were not appreciated by the Dutch government. The Dutch Government recalled Siebold, first to Batavia and then to Holland. Disillusioned by this lack of understanding of Japan and his own failure to be appreciated, von Siebold returned to his native town of Würzburg, offering in vain his services to the French and Russian governments. He died in Munich on October 18, 1866.