Growing energy demand and targets for reducing greenhouse gas emissions are driving a significant hydropower (HP) generation expansion in the Alpine area. However, despite its advantages, HP implementation causes several impacts on the ecological status of river systems and the preservation of characteristic landscapes. The use of decision-making tools, like multi-criteria decision-making (MCDM) methods, can provide helpful support to achieve more sustainable solutions for complex water management problems. In Aosta Valley (NW Italy), an MCDM experimental approach is being applied to define the optimal environmental flow scenario to be released by HP plants, in an attempt to balance energy production needs, economic profitability and environmental safeguard. Four criteria are considered (energy, environment and fishing, landscape, economy) and key stakeholders are involved in the entire decision-making process. However, there is a need to test also other MCDM methodologies in order to understand if an alternative approach could be more suitable for future, more complex, HP management decisions. Therefore, in this paper, seven different MCDM methods are applied to an existing small run-of-the-river HP plant for the selection of the optimal flow release scenario, i.e., SAW, WPM, AHP, TOPSIS, VIKOR, ELECTRE III, and the initially adopted method, SHARE MCA. The results obtained with the application of the different MCDM methods are investigated and statistically compared. The strengths and weaknesses of the different methodological approaches are also discussed. Based on the comparative results and the consequent evaluations, SHARE MCA, WPM, and VIKOR appear to have the most interesting characteristics in terms of overall feasibility.