[8] In 2022, MacLeod revealed that she had been dealing with depression since 2014, and had also been diagnosed with bipolar disorder and a metabolic condition, which requires her to take life long medications.

[10] MacLeod was elected to the Ontario legislature in a by-election that was held to replace John Baird who resigned to run for the federal House of Commons.

[12][13][14] In 2007 MacLeod was satirized by Liberal strategist Warren Kinsella when she was mockingly portrayed in a spoofed picture suggesting she would rather be at home baking cookies than attending a political event with then PC Leader John Tory.

[17] In April 2014, Premier Kathleen Wynne launched a libel lawsuit against MacLeod and PC Party Leader Tim Hudak after they said that she "oversaw and possibly ordered the criminal destruction of [gas plant] documents.

The lawsuit between us, and the comments that led to it, did not reflect our view that the other is in fact a great mother/father, an honourable person and a dedicated public servant.The statement avoided any apology or placement of blame.

MacLeod told reporters that she has been "under enormous pressure from my constituents to seek the federal nomination to replace John Baird", in the new riding of Nepean.

[21] In July 2014, MacLeod became the party's critic for Treasury Board issues, and in October of that year, she became the Vice-Chair for the Standing Committee on Public Accounts.

As Social Services Minister, MacLeod admitted to breaking a Progressive Conservative election promise by cutting the Ontario Basic Income Pilot Project on July 31, 2018.

[24][25] On February 13, 2019, the National Post reported that Ontario Association for Behaviour Analysts (ONTABA) had received a threatening message from MacLeod's office.

[28] On October 31, 2019, Warren Kinsella told The Globe and Mail that his firm provided strategic advice and media training for the government to MacLeod and her political staff in 2018 when dealing with the cuts.

[36] In January 2025, she apologized for alleged Islamophobic social media remarks about Husien Abu-Rayash, a PC nomination candidate for her riding of Nepean.