Midhunam movie is all about Sethumadhavan (Mohanlal) who has plans to start a biscuit factory near his house. But the bureaucracy and the corruption of the officials are the hurdles in front of him. Along with that he has to solve the problems in his family, which his brother (Innocent) and brother-in-law (Jagathy Sreekumar) creates. he marries his long-term fiancée Sulochana (Urvashi) who always cribs that he doesn't have love towards her, which he had shown before their marriage. How sethumadhavan succeeds in his life beating all the odds against him forms the rest of the story.

Nandagopan (Mohanlal) is a respected dance teacher at the Kerala Kala Mandiram (alluding to the famed Kerala Kalamandalam repertory which performs Kerala's temple arts). However, his wife Sumangala (Parvathi) commits suicide, causing him to turn into an alcoholic and a compulsive rule breaker. He is suspected of having killed his wife and is suspended from his job for drunken misbehaviour. The new secretary of the institute Velayudhan (Nedumudi Venu) wants him to be sacked but his former reputation gives him a reprieve. He trains the talented student Malavika (Monisha) to perform in his ambitious composition of the Sita Kalyanam, but her jealous young lover Soman (Vineeth) poisons him.

The story follows Abdullah (Mohanlal) who is hired by the members of a wealthy royal family to assassinate the family head Maharaja Udayavarma (Nedumudi Venu). Abdullah comes into the royal palace under the disguise Ananthan Namboothiri, a classical singer, and tries to use this mask to softly kill the Maharaja.

Kunhikuttan, a famous Kathakali dancer, meets Subhadra, a woman from an upper caste family, who falls in love with his character rather than himself.

Antony, a police officer, disguises himself as a teacher and goes to the school where terrorist Mammen's daughter studies. He sets a trap for Mammen by informing him that his daughter is ill.

Govardhan, a doctor by profession, is wrongly accused of bombing a train and is jailed by the British in Cellular Jail, also known as Kala Pani in Andaman and Nicobar Islands. He witnesses sufferings of hundreds of Indian prisoners there.

Another mission with Mahadevan and crew, as they deal with international terrorism with a flight being hijacked by hardcore terrorists.

Captain Vijay forms a bond with Kumaran, a severely injured man. However, when he dies, Vijay decides to investigate and ends up finding answers related to his life.