The assessment of river health holds paramount significance in diagnosing the conditions of river water environments, and its research serves as a crucial foundation for the functional management and restoration of rivers. We discuss the concept and assessment criteria of health in areas characterized by significant human activity. Utilizing the “over the riverbank” and “under the riverbank” quantification criteria as the framework, a comprehensive river health assessment index system is developed, encompassing seven aspects (riparian zone condition, pollution discharge condition, human–water interaction, physical structure, water environment, water ecology, and socio-economic service function) and 35 indicators. This study introduces the River Health Index (RHI), specifically tailored for regions with significant human activity, facilitating the quantitative assessment of river health status and precise calculation of the River Health Index in these areas. The research employs the RHI to assess the health condition of the Cangzhou section of the Qingliang River in China. The results indicate that the Qingliang River is in a suboptimal state of health, with the key limiting factors being the aspects of “water environment” and “water ecology”. The research demonstrates that the proposed river health assessment system for areas with significant human activity effectively reflects the objective reality of the Qingliang River, exhibiting a high level of reliability and applicability.