In 1993, Brand became a resident panellist, along with Tony Hawks, on BBC monologue show The Brain Drain. Her transition into mainstream television continued when she starred in her own series on Channel 4, Jo Brand Through the Cakehole, co-written with comedy writer Jim Miller, who was already her main stand-up writer. Brand has had several solo television series, and presented shows such as Jo Brand’s Commercial Breakdown. She had a cameo appearance in an episode of Absolutely Fabulous entitled “New Best Friend” (1994), and also appeared on Star Spell, a spin-off from Hard Spell in 2004.

Brand married Bernie Bourke, a psychiatric nurse, in 1997 in Shropshire. They have two daughters, Maisie Bourke and Eliza Bourke. Her husband and two daughters are all vegetarian, but Brand prefers to “pursue pork-pies in service stations when no-one is looking.”

Brand delivered a guest lecture on the subject of psychiatric nursing for the University of Derby Psychology Society in 1997 in return for a donation to Derby Rape Crisis. Also in 1997, she opened, at Lambeth Hospital in South London, the first major exhibition of the Adamson Collection since the death of Edward Adamson, the pioneer of Art Therapy, in 1996.

In 2004, Brand appeared in a special episode of What Not to Wear, where fashion gurus Trinny Woodall and Susannah Constantine gave her a makeover.

Her television success continued with guest appearances on shows such as Have I Got News for You and QI, to the extent where she became the most frequently appearing guest on the latter, appearing in a total of 34 episodes. As a fan of Countdown, Brand achieved an ambition when she was invited to appear in the show’s “Dictionary Corner” as the celebrity guest. She later became a friend of the host, Richard Whiteley, and after his death in 2005 attended his memorial service at York Minster. She has appeared on Countdown as a Dictionary Corner guest 88 times.

In 2007 Brand narrated Laughter & Tears: The Les Dawson Story, a documentary tribute to Les Dawson, which was broadcast on BBC Radio 2 in October 2007.

On 25 March 2007, Brand appeared on Play It Again, where she was required to learn how to play the organ in just four months. This was in preparation to perform Johann Sebastian Bach’s Toccata and Fugue in D Minor for an audience of 8,000 people at London’s Royal Albert Hall on the second largest pipe organ in the United Kingdom. In order to practise her performance, she played Dear Lord and Father of Mankind, a favourite hymn of hers at a church service in her former village church in Benenden, Kent, and accompanied dancers at Blackpool Tower. Prior to this, her only experiences with musical instruments had been childhood piano and violin lessons.

Brand took part in the first celebrity version of Comic Relief Does Fame Academy. In 2007 she appeared as a celebrity contestant on Comic Relief Does The Apprentice. In 2009 she participated in Let’s Dance for Comic Relief, another Comic Relief fundraiser, dancing as Britney Spears, reaching the final. She has also been a judge on the show. In January 2013 Brand took part in a special Comic Relief series of The Great British Bake Off.

On 17 July 2007 Brand was awarded an honorary doctorate for her work as a psychiatric nurse from the University of Glamorgan (now the University of South Wales). Professor Donna Mead, Dean of the School of Health, Sport and Science, who read Brand up for the award commented, “Jo incorporates much of her experience working in the field of mental health into her current work as a comedian. This has increased awareness of the work done by nurses in the mental health field. She has also used her experiences of working with individuals with conditions such as Alzheimer’s to promote awareness of and raise funds for the Alzheimer’s Society.”

In December 2007 she received a Journal of Psychiatric and Mental Health Nursing Lifetime Achievement Award, an award associated with the Eileen Skellern Memorial Lecture. At this event she was praised for making mental health nursing more visible to the general public.

In April 2009 Brand was as a judge with John Amaechi and Jeremy Stockwell on the BBC Two series The Speaker, charting the search for “Britain’s Best Young Speaker”.

In February 2009, Brand was among a group of British entertainers who wrote an open letter to The Times of London in support of the leaders of the Baháʼí Faith who were then on trial in Iran.

In 2010 Brand took part in Channel 4’s Comedy Gala, a benefit show held in aid of Great Ormond Street Children’s Hospital, filmed live at the O2 Arena in London on 30 March.

Brand introduced and spoke at the celebration of Michael Foot’s life at London’s Lyric Theatre, Shaftesbury Avenue, on 8 November 2010. She is also a republican. In January 2012, she gave the South Shields annual lecture at Harton Technology College alongside the MP for the town, David Miliband.

In 2011, Brand presented Jo Brand’s Big Splash, a television programme where she performed a stand-up routine and visited people with a love of water and it was produced by her production company, What Larks! Productions.

Brand is a staunch supporter of the Labour Party. She was still a contributor to and supporter of the party in 2012.

In January 2013 and 2014, Brand was a judge, with Andy Banks and Leon Taylor, on the ITV show Splash! .

On 14 January 2014, Brand presented an episode of The Great Sport Relief Bake Off on BBC Two, a charity version of The Great British Bake Off. In February 2015 she also presented an episode of The Great Comic Relief Bake Off.

She is the presenter of The Great British Bake Off: An Extra Slice, which premiered on 8 August 2014. A second series aired from August 2015, third from August 2016 and a fourth from August 2017.

In 2014, Brand co-wrote and starred as Rose in a comedy pilot for Sky Arts called Damned. The show was commissioned for a full series by Channel 4, airing in 2016; its second series aired in 2018.

In November 2014, Brand was a part of Gareth Malone’s All Star Choir, who released a cover version of “Wake Me Up” to raise money for the BBC’s Children in Need.

In August 2014, Brand was one of 200 public figures who were signatories to a letter to The Guardian opposing Scottish independence in the run-up to September’s referendum on that issue.

In January 2014 Brand was awarded a second honorary doctorate from Canterbury Christ Church University, for her work in raising awareness of mental health issues and challenging the stigma surrounding such illnesses.

In August 2015, Brand judged the first ever Class Clowns competition at the Edinburgh Fringe Festival, she also announced the winner at the Gilded Balloon on the night.

On 28 January 2016, Brand completed a 150-mile walk across Britain, in aid of Sport Relief, in Liverpool. Brand crossed the finish line at the Albert Dock at 7.30pm, having set off from the banks of the River Humber on 22 January. Her efforts were shown in a 60-minute documentary, which aired on 17 March 2016, called Jo Brand’s Hell of a Walk for Sport Relief.

Since 2017, she has presented the Channel 5 series Jo Brand’s Cats & Kittens. The show is available in the United States on Netflix as Kitten Rescuers.

In a 2018 interview, Brand recalled an incident where she was forcibly kissed by a financial trader during a charity event in Canary Wharf, commenting that she chose not to report the incident because ‘it would ruin the day and I was worried no one would believe me’.

On 28 January 2019, the BBC television series Imagine, presented by Alan Yentob, documented Jo’s life and career, with contributions from many of her comedy peers, in a programme titled Jo Brand: No Holds Barred.

In June 2019, Brand was featured in the BBC Radio 4 comedy show Heresy, after a number of European election candidates had been doused with milkshakes during campaign walkabouts the previous month. Brand said “Why bother with a milkshake when you could get some battery acid?” She later added: “That’s just me, sorry, I’m not gonna do it, it’s purely a fantasy, but I think milk shakes are pathetic, I honestly do. Sorry.” The BBC later defended Brand, explaining “the jokes made on Heresy are deliberately provocative as the title implies” and that they were “not intended to be taken seriously.” The Prime Minister at the time, Theresa May, said the BBC should explain why a joke about throwing battery acid was “appropriate content” for broadcast and the BBC later announced that the remark would be edited out of any future broadcasts. The Metropolitan Police confirmed that it had “received an allegation of incitement to violence that was reported to the MPS on 13 June”. and that they were investigating the matter. Appearing at an event in Henley, Oxfordshire, on the same day, the comedian was said to have apologised for making the joke, saying “Looking back it probably was somewhat a crass and ill-judged joke that might upset people.” It was understood that the allegation reported to the police was not made by Nigel Farage or the Brexit Party. Ofcom said it has received 65 complaints about the episode of Heresy. The police dropped the investigation two days later. On 29 August 2019, the BBC’s Executive Complaints Unit (ECU) partially upheld complaints about the joke, saying: ‘Whilst the ECU recognised that the wider message from this episode is an argument for more civility in political discourse, not less, and Ms Brand’s contribution is not intended to be taken as face value, the ECU felt that it went beyond what was appropriate for the show.’