Medicinal plants have served as a principal source of medicine among diverse cultures. Millions of people are affected by liver dysfunction worldwide and its rate continues to increase and remains a global health problem. In Pakistan, several medicinal plants are traditionally used for the treatment of various diseases including liver dysfunction. The present study aims to document the medicinal plants found in four different sites of the Indus ecoregion, used for hepatic dysfunction. Data were collected from four different sites in the Indus ecoregion (Chotiari wetland complex Keti Bunder, Keenjhar, and Pai forests). Forty different villages were surveyed and around 200 people including herbalists (Hakeems) were interviewed (semi-structured interviews and discussions). According to the survey findings, the indigenous people of Indus use 42 wild plant species from 29 families against liver dysfunction. The contribution of the most important families as the hepatoprotective effect was Leguminosae with (21%), Solanaceae and Amaranthaceae with (7%), along with Poaceae and Convolvulaceae (5%) were recorded. Chotiari wetland and Keenjhar Lake have the highest number of plant families that have hepatoprotective plants. Various plants are used for the treatment of liver diseases in many parts of the world including Pakistan; however, safety issues should be evaluated before herbal preparation is prescribed by herbal practitioners or Hakeems.