Doherty was a member of the Meath County Council for the Dunshaughlinlocal electoral area from 2009 to 2011. She was a member of the Oireachtas committees for Health, Finance and the implementation of the Good Friday Agreement during the 31st Dáil. She was also a member of the Constitutional Convention, and was the Chairperson of the Fine Gael committee for health and children. In May 2015, following the claims of IRA involvement of the cover-up of sexual abuse by Máiría Cahill, she was provided with names of a number of alleged abusers which she passed on to the Gardaí who are investigating the issue. She was re-elected to the Dáil at the 2016 general election. She was appointed to the new Dáil reform committee on 22 March 2016. Following the formation of a Fine Gael minority government in May 2016, Doherty was appointed to the cabinet as Government Chief Whip. In July 2017, Doherty confirmed that she had lodged a complaint with the Garda Síochána against political blogger and academic Catherine Kelly. Kelly said that she was cautioned by Gardaí about her social media posts and online articles, which referenced Regina Doherty. In the Dáil it was stated that a US based academic experienced a "sinister and chilling experience" in an Irish airport where she was detained by gardaí and told not to tweet about Ms Doherty or publish any material relevant to her again. On 14 June 2017, she was appointed Minister for Employment Affairs and Social Protection, by TaoiseachLeo Varadkar. In September 2017, it was revealed that she was going to repay an "unlawful" allowance of €15,800 that she received as Government Chief Whip in direct contravention of the law which states that “no allowance can be paid to a party whip if the person is a Minister or Minister of State”. In January 2018, Doherty announced the launch of the consultation process under the review of the Gender Recognition Act 2015, to further expanding the Gender Recognition Act to include those under 18 and non-binary people. In May 2018, Doherty participated in the Opening Plenary Session - Listening Today for Better Social Policies Tomorrow, in the OECD Policy forum in Canada. In January 2019, Doherty briefed the Irish Cabinet, warning that while her department was well fixed to pass emergency legislation to continue social welfare payments in the event of Brexit, the UK may not be. It is understood that the British Government has agreed in principle to continue all payments, although the then Secretary of State for Work and Pensions, Amber Rudd, has been unable to guarantee that the necessary legislation will be passed by 29 March 2019. Also in January 2019, Doherty was appointed director of elections for Fine Gael for the 2019 European elections.
COVID-19 response
Doherty was appointed to the Cabinet Sub-Committee on COVID-19, it published a National Action Plan on 16 March. On 16 March 2020, Doherty announced the COVID-19 Pandemic Unemployment Payment of €350.00, which would be available for six weeks. On 19 March 2020, Doherty announced that all welfare would be distributed each fortnight instead of the traditional weekly, so as to limit the number of people gathering in post offices. On 17 April, she announced that the General Register Office has put arrangements in place for parents to send in their birth registration forms by email or post. Up to then, parents could only register the births of their children by visiting a General Register Office in person, a practice in place since 1864 when the first birth was registered. The first baby to have his birth registered electronically was Aaron Rafferty from Malahide, County Dublin.