Following a brief setback, she established herself with commercial successes in both Bollywood and Kollywood films, including Bombay (1995), Agni Sakshi (1996), Indian (1996), Gupt: The Hidden Truth (1997), Kachche Dhaage (1999), Mudhalvan (1999) and Company (2002).

In 2012, Koirala took a break from acting after being diagnosed with last stage ovarian cancer and underwent an year-long treatment, making a successful recovery by mid-2014.

Koirala spent her early life in India, and she stayed in Varanasi at her maternal grandmother's home for some years and later in Delhi and Mumbai.

[1] In 1991, Koirala made her Hindi film debut with Subhash Ghai's directorial Saudagar, which emerged as a commercial success.

However, this was trailed by a series of films that performed poorly at the box office, including First Love Letter (1991), Anmol and Dhanwan (both 1993), which led to Koirala being labeled "a jinx" by producers.

[17] Koirala's career prospects improved after starring in Vidhu Vinod Chopra's romance film 1942: A Love Story (1994), set during the Indian independence movement.

[18] She played Rajjo, the daughter of a freedom fighter who falls in love with Naren (Anil Kapoor), the apolitical son of a British colonial employee.

[19] Chopra dismissed Koirala as a "terrible actress" after her first screen test, but was impressed with her performance for a second audition and decided to cast her in place of Madhuri Dixit.

[23] In 1995, Koirala made her debut in Tamil cinema with the Mani Ratnam-directed political romance Bombay, starring alongside Arvind Swami.

[24][25] She took up the role on the insistence of her friend Ashok Mehta, at a time when other contemporaries urged her to not act in non Hindi film industries.

[23] The following year, she played a battered wife on the run from her mentally-ill husband in the drama Agni Sakshi, a remake of the Julia Roberts-starrer Sleeping with the Enemy (1991), which begot her positive reviews for her performance.

[36] Featuring Kamal Haasan in dual roles alongside Koirala, Urmila Matondkar and Sukanya, it was the most expensive Indian film at that time, with a budget of ₹150 million.

[45] A critic from Channel 4 wrote, "Koirala in particular is in her element and demonstrates the full range of her acting ability, rather than playing against it as she has had to do in more traditional films".

[48] In a box office roundup of the year, The Indian Express felt Koirala put up an "impressive show" with her successes.

The next year, she went on to collaborate once again with the acclaimed director Mani Ratnam, and starred in his film Dil Se.. (1998) opposite Shah Rukh Khan.

[53] In 1999, she starred in the successful Kachche Dhaage, which was followed by six more releases, the most notable of them being Indra Kumar's drama Mann, remake of 1957 Hollywood classic An Affair to Remember, which entered into the top five highest-grossing films of the year.

Film critic M. Ali Ikram wrote about her performance: "If there is a respite for Manisha's innumerable fans of late, this flick is it.

While filming Laawaris (1999), Koirala began to get tired of her busy schedule and felt "the pressure getting to [her]"; she turned to alcohol for solace and developed anger issues.

The same year, she debuted on television and hosted the reality game show titled Sawaal Dus Crore Ka on Zee TV alongside Anupam Kher.

After starring in moderately successful Chhupa Rustam: A Musical Thriller she next played the protagonist in Rajkumar Santoshi's drama Lajja, along with an ensemble cast that included Rekha, Anil Kapoor and Madhuri Dixit.

In 2008, Koirala starred opposite Irrfan Khan in the family drama Tulsi, in her first leading role since Mumbai Express (2005).

Taran Adarsh from IndiaFM wrote: "Manisha Koirala sinks her teeth in this role and delivers a fine performance.

In 2010, Koirala made her foray into Malayalam cinema with Shyamaprasad's Elektra, a psycho-sensual drama based on Sophocles's ancient Greek tragic play Electra.

She plays the antagonist in the film, which revolves around the concept of the Electra complex, which is a daughter's psychosexual competition with her mother for her father's affection.

"[78] Suhani Singh from India Today noted that she is the "star in this mawkish coming-of-age story", while Stutee Ghosh of The Quint wrote that "Manisha Koirala's grace makes it worth a watch.

"[79][80] In 2018, Koirala featured in one of the segments directed by Dibakar Banerjee in the Netflix anthology Lust Stories, where she played a middle-aged housewife, having an extra-marital affair with her husband's best friend.

[83] Nandini Ramnath of Scroll.in noted, "Manisha Koirala, sporting a deep voice and her nastiest manner, gives a near-parodic role her best shot.

[85] Koirala has advocated the need for an official Earth Anthem for the planet supporting the efforts of Indian poet-diplomat Abhay K in this direction.

[86] In May 2013, after her cancer treatment, Koirala said she intends to use her celebrity status and personal story to inspire others who are battling the dreaded disease.

She was scheduled to speakon "Health is Our Responsibility" at Sneh Foundation in February 2017; on "Cancer is Conquerable" at Apollo Hospitals in Hyderabad; and on "My Life's Lesson" at Shiv Nadar Foundation in Chennai; on "Why Celebrities Need Coaching" in Delhi; on "Woman Empowerment" at National Women's Parliament in Vijayawada; and on "Gifts of Cancer" at TEDx Jaipur.