Objective A set of core index sets applicable to the treatment of ischemic stroke (IS) by traditional Chinese medicine (TCM) has been constructed to IS as a basis for final determination of core index sets. Methods The exploratory sequence design of mixed methods research (MMR) was used to conduct qualitative research first and quantitative research, and the research model of quantitative research was determined based on the qualitative research results. In the qualitative research stage, focus groups composed of TCM encephalopathy and neurology experts, core indicator set methodology experts, clinical pharmacists of encephalopathy and researchers with more than 10 years of experience were selected by purpose sampling method, and focus group meetings were held around the theme of "indicator domain, indicator hierarchy and indicator attribution". Based on the discussion results, the meeting further designed the quantitative research questionnaire. A questionnaire survey was conducted among medical professionals with TCM background nationwide from September 11 to October 11, 2023, using convenient sampling method. Results In the qualitative research stage, 11 categories of IS index domain were successfully divided, including functional impairment evaluation, imaging index, daily living ability evaluation, TCM therapeutic characteristic index and TCM intervention advantage index. In the quantitative research part, 50 valid questionnaires were collected from 23 hospitals in 13 provinces, with a recovery rate of 76.92%. The recovery rate of the second round was 100%. In the end, the initial list of IS indicators in different stages of disease course was developed. The acute stage included 43 second-level evaluation indexes, 8 third-level evaluation indexes and 87 fourth-level evaluation indexes under 8 index domains. The recovery period includes 45 second-level evaluation indexes, 8 third-level evaluation indexes and 72 fourth-level evaluation indexes under 10 index domains. The sequelae stage included 33 second-level evaluation indicators, 8 third-level evaluation indicators and 70 fourth-level evaluation indicators in 9 indicator domains. Conclusion Based on the exploratory sequence design of MMR, this study successfully divide the index domain that IS scientific, in line with the characteristics of the disease and can reflect the characteristics of the intervention effect of TCM, ensuring the scientific and applicability of the initial IS index list, and laying a solid foundation for the construction of a comprehensive, objective and practical core index set.