Aniruddha Guha of Daily News and Analysis described Mukerji's performance in the 2011 film No One Killed Jessica as "one of her best performances till date". Co-starring Vidya Balan, the film was Mukerji's first commercial success since Ta Ra Rum Pum, and was especially noted for being so in the absence of a male star. The film was based on the Jessica Lal murder case, and featured Mukerji as a fictionalised foul-mouthed journalist who is deeply involved with the case. She has described how different the role was from the ones she had previously played, saying, "I actually had to play a man!" Certain critics, however, were critical of her performance, including Anupama Chopra of NDTV, who called her role, "the fatal, false note in No One Killed Jessica," arguing that "the character is written superficially and Rani's portrayal of her is equally banal. It's all about externals. She argues a lot and proudly labels herself a bitch but her hair stays perfectly in place and in the end, she even gets to do a super-hero-like slow motion walk." Even so, the role earned her a third Best Supporting Actress trophy at Filmfare.
Mukerji prefers not to publicise her personal life. She limits her interactions with the media and is sometimes labelled a recluse; she said in a 2011 interview, "Today actors have become more open with the media. But this has posed a problem for actors like me because if I don't do that, then I end up being called reclusive. So now I have changed myself and am easily approachable." Mukerji has collaborated frequently and maintained a close friendship with actors Shah Rukh Khan and Aamir Khan, and filmmaker Karan Johar. The nature of Mukerji's relationship with filmmaker Aditya Chopra was the topic of fervent tabloid reporting in India, though she refused to publicly talk about it. On 21 April 2014, she married Chopra at a private ceremony in Italy. The following year, she gave birth to their daughter Adira. Mukerji has said that she believes in maintaining a work-life balance after motherhood, adding that "it is extremely important for [a mother] to have a career and use her time constructively".
Alongside her acting career, Mukerji is involved with humanitarian causes and is vocal about issues faced by women and children. Mukerji was appointed as an ambassador by Procter & Gamble and the NGO Child Rights and You for their joint venture, Shiksha, to endorse the cause of children's education. In 2011 she set up a Stroke Treatment Fund, in association with the Indian Stroke Association, to pay for the treatment of financially deprived stroke-affected patients. She has made public appearances to support other charities and causes. In March 2004, she visited the Indian army unit in Pokhran, Rajasthan to interact with the jawan troops, for the NDTV reality show Jai Jawan. A decade later, in August 2014, she visited the jawans again at Baramulla. In February 2005, Mukerji and several other Bollywood actors participated in the 2005 HELP! Telethon Concert to raise money for the victims of the 2004 Indian Ocean earthquake. In March 2006, Mukerji celebrated her birthday with the physically challenged children of the Helen Keller Institute; she had previously worked with them while preparing for her role in Black. In November 2010, she was part of a fund raising auction for the "Because I am a Girl" charity campaign. In 2014, Mukerji attended a charity dinner on child abuse in London, where she was felicitated by Prince Charles for raising awareness on the issue through her work in Mardaani.