Direct methanol fuel cells (DMFCs) are gaining attention as a viable technology for portable and remote applications due to the benefits of methanol as fuel. However, the environmental implications of this technology have not been thoroughly evaluated. This study aims to conduct a comprehensive assessment of the environmental impact of a DMFC throughout its entire life cycle, and based on the findings, propose guidelines for minimizing the impact. To eliminate any potential biases, a two-step design methodology is applied. The first step involves obtaining the optimal preliminary design, for which a genetic algorithm is implemented. The second step is to conduct the environmental impact study on that optimal configuration. As a study case, a DMFC for a highly demanding application, such as an unmanned aerial vehicle, is selected, using green methanol as fuel. The results reveal that extraction and production stage has the greatest effect on the environment (74.1%), compared to use (25.8%) and transport stages (0.1%). Among the components of the stack, the catalysts have the most significant environmental footprint, 93.3% of the total impact of the stack during the extraction and production stage, while bipolar plates represent only 5.9%, despite comprising 86% of the stack’s mass.