She was a close associate of J. Jayalalithaa, the late chief minister of Tamil Nadu, who headed the All India Anna Dravida Munnetra Kazhagam (AIADMK) from 1989 until her death in 2016.

Before being imprisoned in the Central Prison in Bangalore, Sasikala appointed Edappadi K. Palanisamy as Chief Minister of Tamil Nadu.

[7] Her nephew T. T. V. Dhinakaran launched Amma Makkal Munnettra Kazhagam in March 2018 as unregistered party, with Sasikala as its general secretary.

These connections helped introduce Sasikala to J. Jayalalithaa, who was the propaganda secretary of the All India Anna Dravida Munnetra Kazhagam (AIADMK) at the time.

[23] Since Sasikala helped cover video of party meetings and distribution of policies of AIADMK through CDs, a friendship developed between the two and they became very close.

[28] P. Chidambaram, who had promised to hold Jayalalithaa and Sasikala accountable, had the latter investigated after assuming the position of finance minister for the union government in June 1996, leading to her arrest under the Foreign Exchange Regulation Act.

In 1999, Sasikala helped organise a tea party for Swamy, who was upset with Vajpayee for not giving him the position of a cabinet minister.

Sasikala then convened the party's MLA council in her capacity as the general secretary, where Edappadi K. Palaniswami was unanimously appointed as the new chief minister and sworn in the next day.

[1] Sasikala filed a case in the City Civil Court IV of Chennai in February 2021, but it upheld her dismissal as the AIADMK general secretary in April 2022.

[49] She later attempted to regain her political influence and released audio tapes on social media, calling on people to bring in a government modelled after Jayalalithaa's policies and push out "enemies and traitors".

She also claimed that she stayed away from the AIADMK so Palaniswami and Panneerselvam would win the local elections and promised to unite the disputing factions of the party.

[52] A commission probing Jayalalithaa's death recommended investigating Sasikala and others in a report submitted to the state government in August 2022.

[54] After his expulsion was overturned by the Madras High Court in August 2022, Panneerselvam stated that he would meet with Sasikala and Dhinakaran to unite the AIADMK.

[55] On 2 September 2022, a division bench of the Madras High Court upheld the decisions of the AIADMK general council meeting held on 11 July 2022 and set aside the previous court order of the single judge in the appeal case of Edappadi K. Palaniswami, thus effectively restoring unitary leadership.

[58][59] After the AIADMK lost by a huge margin in the 2024 Indian general election held in Tamil Nadu, Sasikala announced her return to politics and blamed "certain selfish people" within the party for its defeat.

[65] The Supreme Court refused her plea to surrender after a fortnight and to be allowed to have food from home,[66] so Sasikala and Ilavarasi presented themselves for imprisonment on 15 February 2017.