A novel integrated approach is developed to quantitatively evaluate the extracellular polymeric substances (EPS) extraction efficiency after taking into account EPS yield, EPS damage, and cell lysis. This approach incorporates grey relational analysis and fuzzy logic analysis, in which the evaluation procedure is established on the basis of grey relational coefficients generation, membership functions construction, and fuzzy rules description. The flocculation activity and DNA content of EPS are chosen as the two evaluation responses. To verify the feasibility and effectiveness of this integrated approach, EPS from Bacillus megaterium TF10 are extracted using five different extraction methods, and their extraction efficiencies are evaluated as one real case study. Based on the evaluation results, the maximal extraction grades and corresponding optimal extraction times of the five extraction methods are ordered as EDTA, 10 h > formaldehyde + NaOH, 60 min > heating, 120 min > ultrasonication, 30 min > H2SO4, 30 min > control. The proposed approach here offers an effective tool to select appropriate EPS extraction methods and determine the optimal extraction conditions.