She became Kenya's first high-profile athlete to fail a test when she tested positive for the performance-enhancing drug EPO in 2014.
Jeptoo, 33, says she may have been prescribed banned substances at a local hospital after a road accident.
The ruling means she forfeits her 2014 Boston and Chicago Marathon titles.
She is now banned until 30 October 2018 and has also been fined 15,000 Swiss francs (£12,396) as a contribution to the IAAF's legal fees and expenses.
Kenya has been in the spotlight for the past two years after a German television programme claimed many athletes from the east African nation are doping.
Jeptoo, one of most successful runners in Kenyan history, was due to be crowned World Marathon Major Champion for 2014 but the ceremony was called off soon after news of her failed test.
Kenyan marathon runner Rita Jeptoo has had her two-year ban doubled after an IAAF appeal was upheld by the Court of Arbitration for Sport.