He formerly served as the general secretary of Jamiat Ulama-e-Hind (JUH), and as member of the Rashtriya Lok Dal (RLD) party in the Rajya Sabha (the Indian upper house) in the state of Uttar Pradesh from 2006 to 2012.

[6] Madani led JUH relief and advocacy efforts in the aftermath of the 2001 Gujarat Earthquake and the subsequent period of ethno-religious violence in 2002.

[9] He later led a march of over 10,000 protestors to the Prime Minister's Residence in Delhi on 15 October 2002 to protest against ethno-religious violence inflicted upon the Muslim community.

[12][13] Madani was active in the leadership of the Ganaunnayan Janadhikar Sangram Committee (an alliance of 22 local and national organisations) during the period of civil unrest in Nandigram in 2007.

[14] He also launched an anti-terrorism campaign through the JUH in 2008, which involved the issuing of a Fatwa by his alma mater Darul Uloom Deoband in May 2008, which condemned terrorist activity as anti-Islamic.

The conferences were attended by approximately 200 Islamic scholars and religious leaders from multiple countries, including the Maldives, Britain, Pakistan and Myanmar, and advocated for peaceful, dialogue-based solutions to conflicts, as well as the reiteration of the anti-terrorism Fatwa issued by Darul Uloom Deoband in 2008.

[42] In July 2018, Madani established the Jamiat Youth Club (affiliated with the JUH), which was modelled after the Bharat Scouts and Guides organisation.

[43] Following the abrogation of Article 370 on 5 August 2019 and the subsequent period of civil unrest in Kashmir, Madani convened a meeting of leading Muslim organisations and religious leaders in India through the JUH, where he co-sponsored a unanimous resolution that questioned the way of abrogating Article 370, called for the restoration of normalcy and the protection of human rights in Kashmir, while also supporting the integrity and stability of India.

[50] On 6 October 2019, Madani criticised Amit Shah for his role in the National Register of Citizens (NRC), and the Citizenship (Amendment) Act, 2019 (CAA).

[55][56] During the initial phase of the COVID-19 pandemic in India, Madani offered the use of 10,000 isolation centres in a letter to the Prime Minister, Narendra Modi.