Tangled Sisters revolves around Jeevika and Manvi Chaudhary who live in Rishikesh. Orphaned as small girls, they are brought up in an environment that tests their abilities to adapt in life. Jeevika is the older of the two and often finds herself having to solve the messes that the mischievous Manvi gets herself in as well as the problems she causes for others.
Jeevika marries Viren, the son of an elite family of lawyers, and she leaves for Chandigarh to live with his family. Meanwhile, his brother Virat begins to fall for Manvi, who soon starts to reciprocate those feelings.
Manvi falls ill with leukaemia and needs a bone marrow transplant to survive. Jeevika, Virat and Manvi go to Mumbai to start Manvi’s treatment. Meanwhile, Jeevika gets pregnant, but is left with no other choice than aborting her baby to save Manvi, as she is the only perfect bone marrow match. Following her successful treatment, Manvi and Virat get married, and Virat pursues his true passion and a career in music. Both the sisters later have a daughter each, Mansi and Jahnvi.