Introduction Although the Tibetan medicine Triphala (THL) is widely used in many countries, insufficient progress has been made in quality control. Objectives The present study aimed to propose a methodology for quality control of THL based on HPLC fingerprinting combined with an orthogonal array design. Methods Seven identified peaks were used as indicators to examine the effects of temperature, extraction time, and solid–liquid ratio on the dissolution of active ingredients in THL. Fingerprint analysis was performed on 20 batches of THL from four geographical areas (China, Laos, Thailand, and Vietnam). For further chemometric assessment, analysis techniques including similarity analysis, hierarchical clustering analysis, principal component analysis, and orthogonal partial least squares discrimination analysis (OPLS‐DA) were used to classify the 20 batches of samples. Results Fingerprints were established and 19 common peaks were identified. The similarity of 20 batches of THL was more than 0.9 and the batches were divided into two clusters. Four differential components of THL were identified based on OPLS‐DA, including chebulinic acid, chebulagic acid, and corilagin. The optimal extraction conditions were an extraction time of 30 min, a temperature of 90°C, and a solid–liquid ratio of 30 mL/g. Conclusion HPLC fingerprinting combined with an orthogonal array design could be used for comprehensive evaluation and quality assessment of THL, providing a theoretical basis for further development and utilization of THL.