The success of Panchathanthiram lies in its relatable characters and situational comedy. The film's protagonist, Krishna, is an ordinary man with whom audiences can identify. The supporting cast, including Yogi Babu and Bhanu Sree, add to the comedic charm. The film's climax, which revolves around a twist in Krishna's relationships, is well-executed and satisfying.

The second half of the film involves the friends trying to hide their "crime" from their suspicious wives and the police while attempting to reunite Ram and Mythili. In the end, it is revealed to be a bedtime story Mythili is telling their baby, and the couple lives happily ever after.