Although construction of reservoirs and dams is one of the most common approaches to satisfy water demand and alleviate water scarcity, this approach severely affects river ecosystems. The most direct impact of human activities on rivers, for instance, regulating river can lead to degraded riverine ecosystems as part of the hydrological alteration. This paper determines the available ratio of water resource of natural or semi-natural rivers for ecological feasible regions using a method that transcends the traditional perspective of designed environmental flow. Our framework involves a modified percent of flow approach to identify the ecological feasible region of water resources utilization, which sequentially acts as a constraint for a reservoir optimization model based on the Cuckoo Search algorithm to obtain an optimal diversion process. Indicators of the hydrological alteration statistical method and the histogram matching approach are used to examine the framework's performance. The Han to Wei inter-basin water transfer project of China is selected as a case study. Results indicate that: (1) the allowable diversion rate with this modified percent of flow approach is more effective for reducing interference of diversion on the ecosystems than the conventional planned diversion rule; water demand, however, cannot be satisfied by the allowable diversion rate; (2) ecological feasible region is an accessible constraint for reservoir operation model, and the optimal diversion rate of such model is a trade-off output between the human water demand and the riverine ecosystems protection; and (3) increased allowable diversion rates alter flow indicators including the February flow, 30-day minimum flow, and low pulse count more appreciably than does the optimal diversion rate. This study provides key insights on how to achieve a trade-off between human water demand and riverine ecosystems protection, therefore contributing to the local sustainable development of social economy and ecological environment.