Abstract Sustainability is an important and difficult consideration for the stakeholders/decision-makers when planning a biofuel supply network. In this paper, a Mixed-Integer Non-linear Programming (MINLP) model was developed with the aim to help the stakeholders/decision-maker to select the most sustainable design. In the proposed model, the emergy sustainability index of the whole biodiesel supply networks in a life cycle perspective is employed as the measure of the sustainability, and multiple feedstocks, multiple transport modes, multiple regions for biodiesel production and multiple distribution centers can be considered. After describing the process and mathematic framework of the model, an illustrative case was studied and demonstrated that the proposed methodology is feasible for finding the most sustainable design and planning of biodiesel supply chains.