[6] On June 1, 2005, President Arroyo appointed Duque as secretary of the Department of Health because of his efficient leadership at the helm of PhilHealth.

[8] During his tenure, the World Health Organization (WHO) cited the Philippines for being one of only three nations that had excellent risk communication strategies against the deadly AH1N1 virus.

[8] Duque also served concurrently as the Anti-Hunger Czar via his role as Chair of the National Nutrition Council (NNC), tasked by the President to oversee the implementation of the hunger mitigation programs of 27 government agencies.

[15] Duque, as Health Secretary, has led reforms in improving the information technology system of PhilHealth to safeguard against fraudulent claims and other forms of cybercrime.

[16] Duque has also been an outspoken champion for raising vaccination rates among children and youth to combat highly contagious diseases such as polio and measles.

[17] He has urged parents, health workers, and local governments to fully participate in the synchronized polio vaccination in order to stop the disease.

[18] Duque moved for the historic passage of two major pieces of legislation – the Universally Accessible, Affordable Quality Medicine Act of 2008 and the Food and Drug Administration Law of 2009.

On July 29, 2019, in his privilege speech, Senator Panfilo Lacson accused Duque of an alleged conflict of interest as secretary of the Department of Health.

[20] According to Lacson, DPI continued to earn millions of pesos from the government through the lease of an EMDC building for the use of the Philippine Health Corporation Regional Office 1 in Dagupan City.

Before the outbreak in the Philippines, while cases were surging in China, Duque told the House of Representatives that while a temporary ban on Chinese tourists has been among the options studied by the government, there may be serious "political and diplomatic repercussions" with such a move.

[25] In a press briefing held on April 9, 2020, Duque noted that the number of confirmed COVID-19 cases in the Philippines is "relatively low" compared to other countries, despite limited testing and running contrary to earlier statements released by the Department of Health.

His special assistant, Beverly Ho, earlier said in a virtual press briefing that the impact of the ECQ would only be learned by mid-April as it was too early to tell whether it had a role in curbing the spread of the coronavirus.

362 calling for Duque's immediate resignation for his "failure of leadership, negligence, lack of foresight, and inefficiency in the performance of his mandate as the secretary of the Department of Health.