In February 2004, Muraleedharan was appointed Minister of Power in the A. K. Antony Ministry, though he was not a member of the Kerala Legislative Assembly.[5] He was required to win a seat within six months to continue as the minister but lost in by-election from Wadakkancherry. Subsequently, he resigned in May that year. He is the only state Minister who was never MLA and never faced the legislative assembly.[6]
However, for the Kerala Assembly elections of 2006, DIC(K) made a pact with UDF as LDF declined to make any electoral arrangements with DIC(K). DIC(K) contested in 17 constituencies but managed to get elected only from one seat mostly because of grassroots level cross-voting by Congress. Muralidharan lost the election in Koduvally constituency to P.T.A. Rahim.
With the future of the DIC(K) party untenable, some party members of the DIC(K) returned to the Congress party whilst others, including Karunakaran and Muraleedharan, decided instead to join the Nationalist Congress Party (NCP).
Later, Karunakaran rejoined the Congress party, while his son Muraleedharan opted to stay with the NCP, decrying his father's "betrayal".[7] Muraleedharan contested the 2009 Lok Sabha polls from the Wayanad constituency under the NCP ticket, but came only in third place, behind the Congress party and the CPI.[8]
In August 2009, he was expelled from the NCP and sacked as state chief of the party, as he openly expressed his desire to rejoin the Congress party.[9] He was subsequently refused re-entry into the Congress party, the party leadership stating that the disparaging comments he had made about the party leadership whilst in opposition were too big a barrier to his re-joining.[9][10] Muraleedharan pledged that he would "wait for any length of time" for the party to change its mind and readmit him, while his father Karunakaran stated that he would take up the matter with the national leadership of the Congress party, if necessary.[9] He was readmitted to the Congress party in February 2011, after his father died, and was given a ticket to contest the Assembly election from the Vattiyurkavu Assembly constituency (former Thiruvananthapuram North Constituency). Subsequently, he won his first assembly election after he defeated ruling Communist Party of India-Marxist (CPI-M) supported independent candidate Cherian Philip by a margin of over 16,167 votes on 14 May 2011.[11] He was re-elected for the second time in 2016 defeating Kummanam Rajasekharan of Bharatiya Janata Party by a margin of 7622 votes.