The team at the National Museum of American History said Thursday the conservation effort will cost about $225,000 from public and private funds, The Washington Post reported.
The Bible stayed in the Jefferson family until the Smithsonian bought it from a great-granddaughter for $400 in 1895.
Jefferson never allowed the book to be published during his lifetime. It was published in 1895 by Jefferson's grandson, Thomas Jefferson Randolph.
As outlined in an 1803 letter to Joseph Priestly, "The Life and Morals of Jesus of Nazareth" was conceived by Jefferson as a personal exploration covering the "deism and ethics of the Jews" and concluding with the "principles of a pure deism" taught by Jesus, "omitting the question of his deity."
He eventually altered his vision creating a personal document, sitting by candlelight in Monticello, using a razor to cut and paste passages of the New Testament from six books in four languages to sculpt his own religious work -- not without criticism.
"This is a private document he created for himself," said Harry R. Rubenstein, chairman of the Smithsonian's political history division. "He never sold it because he didn't want it to be public. He wanted to avoid bringing back the arguments that he was anti-Christian."
The pages have verses glued on each side and are brittle with age with 90 percent showing at least some damage, but the hand-sewn binding is tight, making for a rigid spine, the Post said.
"There are 12 different types of paper and seven different types of ink," said Janice Stagnitto Ellis, the museum's paper conservator. "We took tiny samples of ink from the ruled line. The paper fibers are weak."
Once the conservation effort is complete, the Bible will go on display at the museum for four months beginning in November.